Jennifer L. Macdonald
May 1, 2005; 46:1061-1067
Methods

W Gamble
Nov 1, 1978; 19:1068-1070
Articles

M el-Saadani
Apr 1, 1989; 30:627-630
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Mohamad Navab
Sep 1, 2000; 41:1495-1508
Articles

Mohamad Navab
Sep 1, 2000; 41:1481-1494
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M. Burstein
Nov 1, 1970; 11:583-595
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JL Dixon
Feb 1, 1993; 34:167-179
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Vitali Matyash
May 1, 2008; 49:1137-1146
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AE Christian
Nov 1, 1997; 38:2264-2272
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Jason M. Ridlon
Feb 1, 2006; 47:241-259
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Chatham House appoints Tim Benton as Research Director for Energy, Environment and Resources News Release sysadmin 30 May 2019

Chatham House is pleased to announce that Professor Tim Benton has been appointed as research director of the Energy, Environment and Resources Department.

Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy News Release sysadmin 18 November 2019

The 2019 Chatham House Prize is awarded to Sir David Attenborough and Julian Hector, head of BBC Studios Natural History Unit, for the galvanizing impact of the Blue Planet II series on tackling ocean plastic pollution.

Chatham House Prize: Malawi Judges Win for Election Work News Release NCapeling 23 October 2020

Malawi’s constitutional court judges have won the 2020 Chatham House Prize in recognition of their 'courage and independence in the defence of democracy'.

Deplatforming Trump puts big tech under fresh scrutiny Expert comment NCapeling 22 January 2021

The response of digital platforms to the US Capitol riots raises questions about online content governance. The EU and UK are starting to come up with answers.

The ‘deplatforming’ of Donald Trump – including Twitter’s announcement that it has permanently banned him due to ‘the risk of further incitement of violence’ after the riots in the US – shows once more not only the sheer power of online platforms but also the lack of a coherent and consistent framework for online content governance.

Taking the megaphone away from Trump during the Capitol riots seems sensible, but was it necessary or proportionate to ban him from the platform permanently? Or consistent with the treatment of other ‘strongmen’ world leaders such as Modi, Duterte and Ayatollah Ali Khamenei who have overseen nationalistic violence but whose accounts remain intact?

Such complex decisions on online expression should not made unilaterally by powerful and unregulated tech actors, but instead should be subject to democratic oversight and grounded in the obligations of states and responsibilities of companies under international human rights law.

The speed and scale of digital information has left governments across the world struggling with how to tackle online harms such as hate speech, extremist content and disinformation since the emergence of mass social media 15 years ago.

The US’s hallowed approach to the First Amendment, under which speech on public issues – even hate speech – occupies the highest rank and is entitled to special protection, has contributed to a reluctance to regulate Silicon Valley’s digital platforms. But the irony is that by not regulating them, the government harmed freedom of expression by leaving complex speech decisions in the hands of private actors.

Meanwhile at the other extreme is the growing number of illiberal and authoritarian governments using a combination of vague laws, censorship, propaganda, and internet blackouts to severely restrict online freedom of expression, control the narrative and, in some cases, incite atrocities.

Regulation is on the way

The happy medium – flexible online content regulation providing clarity, predictability, transparency, and accountability – has until now been elusive. But even before the deplatforming of Trump, 2021 was set to be the year when this approach finally gained some traction, at least in Europe.

The EU’s recently-published draft Digital Services Act puts obligations on dominant social media platforms to manage ‘systemic risks’, for example through requirements for greater transparency about their content decisions, algorithms used for recommendations, and online advertising systems.

The UK will shortly publish its Online Safety Bill, which will establish a new regulatory framework for tackling online harms, including the imposition of a duty of care and codes of conduct on Big Tech, to be overseen by an independent regulator (Ofcom).

Both proposals are based on a ‘co-regulatory’ model under which the regulator sets out a framework substantiated with rules by the private sector, with the regulator performing a monitoring function to ensure the rules are complied with.

Both also draw on international human rights standards and the work of civil society in applying these standards in relation to the online public square, with the aim of increasing control for users over what they see online, requiring transparency about tech companies’ policies in a number of areas, and strengthening the accountability of platforms when they fall foul of the regulation.

The procedure for both proposals has also been inclusive, involving extensive multi-stakeholder consultations with civil society organizations and Big Tech, and the proposals will be subject to scrutiny in 2021, notably from the EU and UK parliaments.

Both proposals are at an early stage, and it remains to be seen whether they go far enough – or indeed will have a chilling effect on online platforms. But as an attempt to initiate a dialogue on globally coherent principles, they are positive first steps. They also provide food for thought for the new Joe Biden administration in the US as it turns its attention to the regulation of Big Tech.

For some time civil society – most prominently David Kaye, the former UN Special Rapporteur on freedom of expression and opinion – have called for content regulation to be informed by universal international human rights law standards.

The EU and UK are peculiarly well-placed to take the lead in this area because European countries have for decades been on the receiving end of judgments from the European Court of Human Rights on the appropriate limits to freedom of expression in cases brought under the European Convention on Human Rights.

In deciding these cases, the court has to balance the right to freedom of expression against the restrictions imposed – for example in the context of incitement to violence, political debate, and satire. Deciding where to draw the line on what can and cannot be expressed in a civilised society which prizes freedom of expression is inevitably a difficult exercise.

International human rights law provides a methodology that inquires whether the interference to freedom of expression was prescribed by law and pursues a legitimate aim, and also whether it was necessary in a democratic society to achieve those aims – including whether the interference was necessary and proportionate (as for example in Delfi AS v Estonia, which involved a news portal failing to take down unlawful hate speech).

To be effective, online content regulation has to bite on tech companies, which is a challenge given the internet is global but domestic law normally applies territorially. The EU’s proposals have an extraterritorial element as they apply to any online platforms providing services in the EU regardless of where the platform is headquartered.

Further, both the EU and UK want to give the regulator strong enforcement powers – it is proposed for example that Ofcom will have powers to fine platforms up to ten per cent of their turnover for breaches.

Although the proposals would not apply directly to the deplatforming of Trump which occurred in the US, the philosophy behind the EU and UK approach is likely to have an impact beyond European shores in promoting a co-regulatory model that some of the bigger tech companies have been inviting for some time, reluctant as they are to ‘play God’ on content moderation decisions without reference to any regulatory framework.

In the absence of regulation, the standards of tech platforms such as Facebook and Twitter have already evolved over time in response to pressure from civil rights groups, users, and advertisers, including updated policies on protecting civic conversation and hate speech.

Facebook has also set up an independent Oversight Board, whose members include leading human rights lawyers, to review decisions on content including – at its own request – the decision to indefinitely suspend Trump from Facebook and Instagram. Decisions on the Board’s first tranche of cases are expected imminently.

Gatekeeper status is key

Online content regulation also needs to address the role of Big Tech as the ‘digital gatekeepers’, because their monopoly power extends not just to editorial control of the news and information we consume, but also to market access.

The decision of Apple, Google, and Amazon to stop hosting right-wing social network Parler after it refused to combat calls for violence during the US Capitol riots was understandable in the circumstances, but also underlined the unilateral ability of Big Tech to decide the rules of the market.

Again, it is Europe where efforts are underway to tackle this issue: the EU’s draft Digital Market Act imposes obligations on online gatekeepers to avoid certain unfair practices, and the UK’s new Digital Markets Unit will have powers to write and enforce a new code of practice on those technology companies with ‘substantial and enduring’ market power.

In the US, Biden’s team will be following these developments with interest, given the growing bipartisan support for strengthening US antitrust rules and reviving antitrust enforcement. The EU’s recently published proposals for an EU-US tech agenda include a transatlantic dialogue on the responsibility of tech platforms and strengthened cooperation between antitrust authorities on digital markets.

Ultimately a consistent – and global – approach to online content is needed instead of fragmented approaches by different companies and governments. It is also important the framework is flexible so that it is capable of applying not only to major democracies but also to countries where too often sweeping state regulation has been used as a pretext to curtail online expression online.

The pursuit of a pluralistic framework tailored to different political and cultural contexts is challenging, and international human rights law cannot provide all the answers but, as a universal framework, it is a good place to start. The raft of regulatory measures from the EU and UK means that, regardless of whether Trump regains his online megaphone, 2021 is set to be a year of reckoning for Big Tech.

Implications of post-COVID-19 Restructuring of Supply Chains for Global Investment Governance 14 July 2020 — 9:00AM TO 10:30AM Anonymous (not verified) 9 February 2021 Online

As companies rethink and diversify their supply chains in order to enhance resilience, what will this mean for current and future global investment governance?

What are the risks of negative effects on inclusivity and transparency? Does this shift create an opportunity to advance good governance of cross-border investment practices?

This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world.

Insights from Climate Policy: Engaging Subnational Governments in Global Platforms 10 June 2020 — 2:45PM TO 6:00PM Anonymous (not verified) 9 February 2021 Online

How have subnational governments shaped the global agenda and created momentum on climate change where national and international governance processes could not?

Can these advances be converted into meaningful collaboration channels for policy development? What works, or does not, when it comes to engagement with multilateral negotiation processes? What ingredients are necessary for success? What are the broader implications of these trends for inclusivity and innovation in international governance?

This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world.

Geopolitical shifts and evolving social challenges – what role for human rights? 29 June 2021 — 3:00PM TO 4:30PM Anonymous (not verified) 10 June 2021 Online

Speakers reflect on some of the key themes that will influence the future of human rights.

Please click on the below link to confirm your participation and receive your individual joining details from Zoom for this event. You will receive a confirmation email from Zoom, which contains the option to add the event to your calendar if you so wish.

Shifts in geopolitical power and the rise of authoritarianism are disrupting the dynamics for making progress on human rights globally.

At the same time, the relevance of the global human rights framework is being called into question by some of our most acute social challenges – rapidly evolving technology, deepening inequality and the climate crisis.

Chatham House’s Human Rights Pathways project is exploring how alliances, strategies and institutions are adapting, and will need to evolve, to strengthen human rights protection in this increasingly contested and complex global environment.

At this panel event speakers reflect on some of the key themes that will influence the future of human rights, including the long-term impacts of the pandemic, the place of human rights diplomacy in the new geopolitics, the relevance of human rights to social movements, and the potential of human rights law to galvanise efforts on urgent challenges such as the climate crisis.

Counter-terrorism measures and sanctions: How to avoid negative consequences for humanitarian action? 9 September 2021 — 2:00PM TO 3:30PM Anonymous (not verified) 21 July 2021 Online

Exploring current endeavours to address the tensions between counter-terrorism measures, sanctions and humanitarian action.

Counter-terrorism measures  address broad forms of support to terrorist acts. Their expansion, internationally and domestically, has given rise to new points of friction with international humanitarian law. Unless the measures include adequate safeguards, they  can impede humanitarian action. Country-specific sanctions imposed for other objectives, such as ending conflicts or protecting civilians, raise similar challenges for humanitarian action. 

These problems are not new, but solutions at international and national level remain elusive. 

At this panel event, which marks the launch of a new Chatham House research paper, panellists explore current endeavours to address the tensions between counter-terrorism measures, sanctions and humanitarian action.

• What are the current dynamics and developments at Security Council level?  
• What are the opportunities now that the UK is developing its independent sanctions strategy? 
• What challenges do counter-terrorism requirements in funding agreements for humanitarian action  pose? 
• What is necessary to make progress?

Re-imagining trade for domestic and foreign policy Expert comment NCapeling 7 December 2021

Exploring future trade policy through issues such as the green transition, labour standards, human rights, the role of the WTO, and non-trade policy objectives.

Balancing trade and non-trade policy objectives

Marianne Schneider-Petsinger

The supply chain disruptions stemming from the COVID-19 pandemic highlight trade cannot be taken for granted, and economic interdependencies have both benefits and costs. As international commerce rebounds and trade policy is increasingly seen through the prism of enhancing resilience, the moment is ripe to redefine and reimagine trade.

The goal of trade policy has never been to increase trade for trade’s sake, so a new narrative and framework for global trade requires striking a careful balance between pursuing trade and non-trade policy objectives.

Protecting the environment, strengthening labour standards, and upholding human rights have long been goals for which trade policy is used as a lever, and the interaction of trade and national security interests as well as the links between trade and competition policy are not new issues either.

All these non-trade policy aspects have come to the forefront as the geopolitical context has shifted and the transition to green and digital economies has gathered force – and, at times, these different non-trade policy goals clash.

The US and European Union (EU) are promoting solar energy to fight climate change but supply chains for solar panels are heavily reliant on forced labour from Xinjiang, and hence it is not yet certain whether environmental or human rights concerns will prevail. However, it is clear trade policy tools can be part of a comprehensive solution which manages inherent tensions while still advancing both objectives.

Trade policy is also not just a foreign policy instrument but links closely to domestic policy – the populist backlash against globalization in much of the developed world, especially the US and Europe, was in part driven by anti-trade sentiment.

While American attitudes towards trade improved after the 2016 election of Donald Trump, positive views towards trade dropped sharply in 2021. The Biden administration’s worker-centred trade policy aims to address distributional effects of international economic integration which is a long-standing challenge. Thus, tackling non-trade policy issues without losing sight of this unresolved core issue requires careful calibration.

Trade policy is being pulled in many different directions at the same time as the core institution governing global trade – the World Trade Organization (WTO) – is in crisis, and it is uncertain how much of the non-trade policy agenda the WTO can handle. If the linkage to non-trade policy becomes too strong, this could be the straw that breaks the WTO’s back, but if it is too weak, the WTO risks becoming irrelevant in efforts to tackle key global challenges.

But if its 164 members can generate trade-oriented solutions to non-trade issues, they can revive the organization and mobilize domestic support for global trade at the same time. This balancing act in managing the tensions between trade and non-trade policy objectives lies at the centre of future-proofing trade policy and global trade governance.

Developing countries must be part of green trade revolution

Carolyn Deere Birkbeck

The biggest challenge in taking environmental efforts forward within the multilateral context is to successfully combine environmental ambition with an approach which engages developing countries as partners, reflects their environment-related trade priorities, and addresses their sustainable development interests.

The importance of engaging developing countries must not be underestimated because it is vital a global green economy does not leave the poorest behind, or becomes two-tier where green trade happens only between certain countries and the essential task of incentivizing and supporting sustainable production and consumption patterns in all countries is neglected.

The new member-led initiatives at the WTO do signal that, while the rulemaking and negotiating functions remain central to the global trade body, governments recognize the need for enhanced, transparent, and inclusive policy dialogue as well as problem-solving on sectoral issues and specific trade-related challenges.

Given the well-documented challenges of achieving multilateral consensus at the WTO, governments are exploring new ways to work within multilateral frameworks and to redefine what progress and successful outcomes should look like.

Therefore, there is a need for best practices, voluntary action, pledges, and guidelines to both sustain the relevance of the multilateral trading system and support policy action at the national level for trade which underpins environmental and wider sustainable goals.

Making progress on an environmental agenda which reflects sustainable development concerns requires stronger leadership, engagement, and advocacy from business, civil society, and research communities in both developing and developed countries, as well as economies in transition.

Meaningful, inclusive dialogue and action at the WTO also requires deeper efforts to build policy coherence among environment, development, and trade policymaking at home, with environmental ministries having a key role to play in bringing expertise to bear and ensuring strong regulatory environments and institutions for the implementation of national, regional, and international environmental commitments.

But at the domestic level, many countries still have to overcome complex politics and diverse interests as they work to transform their economies toward greater sustainability and tackle the costs of transition.

Social preparation holds the key to trade transitions

Bernice Lee 

Trade being often depicted as the mother of all ills should not come as a surprise, as politicians are only too happy to put the blame on trade when all sorts of exogenous shocks, such as technological change, could actually be the trigger which fires the bullet into local industries or jobs.

Admittedly trade does have a way of breaking the seams in the social fabric but the fact politicians often ignore negative impacts of trade means its benefits can be likened to Schrodinger’s cat, both real and illusive. But trade being mainly depicted as a ‘zero-sum’ pursuit and trade deals as the result of swashbuckling duels belie the reality that the real business of trade is often boring, bureaucratic, but necessary.

This is particularly true when trade provides access to a much larger variety of necessary products, such as medicine, food, and minerals, which can be expensive to make domestically. Selling products and services abroad also brings in the hard currency needed to buy these goods or to spend on trips abroad.

This does not take away the fact trade is extremely disruptive but, as a result of all the theorizing and understandable rants about trade, large swathes of the international community have effectively foregone it as a force for good or as an instrument which – while not the answer to all problems – can help smooth the path to well-being through efficiency gains and income growth, as well as putting to work the theory of comparative advantage as promised by the textbooks.

Alas, what the textbooks do not clearly spell out – until recently – is that trade brings positive benefits only if a society is ready for trade, which often means having the cushion for social protection such as healthcare, unemployment benefits, and opportunities for training and reskilling.

The ‘China shock’ literature vividly depicts how workers rarely seamlessly move from one job or sector to another and so, without adequate social protection, trade not only magnifies existing fractures, it also exacerbates inequality. As the aftershock lingers for decades, the lesson learned is the importance of social readiness for trade, especially the role played by governments in providing support for workers as part of the adjustment to trade and globalization.

Authors of this China shock literature recently suggested the next shock will be the transition from fossil fuel production, but the good news is this so-called ‘just transition’ challenge is one which proponents of green energy are well aware of.

But ultimately the China shock could be the dry run for the advent of machine intelligence, meaning better preparation is needed with solid social policies, investment in institutional readiness, and social preparedness to ensure the machines only take on monotonous and unsafe work – not our livelihoods and communities.

Trading partners must move to creating human rights impact

Dr Jennifer Zerk

The question of whether, and how, trade policy should be used as a way of addressing human rights concerns remains controversial and attempts to link the two still attract accusations of ‘protectionism’ and ‘neo-colonialism’.

Momentum appears to be behind those arguing for greater alignment between trade policy and human rights objectives – a trend which is most noticeable in the increasing willingness of trade partners to reference human rights standards in their trade agreements and in the growth of complementary activities such as human rights impact assessment and monitoring.

Evidence that these are having an impact ‘on the ground’ remains elusive. Nevertheless, efforts to enhance scrutiny of trade agreements from a human rights perspective, and to signal the importance of respect for human rights to a trading relationship, can still have value.

Even if causal relationships between trading arrangements and human rights impacts are difficult to establish conclusively, human rights impact assessment and subsequent monitoring activities provide valuable opportunities for stakeholders to weigh in on aspects of trade policy which are of concern.

Such processes not only help governments to realize rights of public participation, they also contribute to good governance by making it more likely that potential human rights problems will be recognized and addressed.

Turning to the agreements themselves, various ideas have been put forward on how to make these more responsive to human rights concerns.

Options mooted by EU institutions in recent years include an enhanced monitoring and enforcement role for consultative bodies established under specialized ‘trade and sustainable development’ chapters, and better mainstreaming of human rights commitments in sector-specific chapters.

However, given the political and resource-related difficulties in developing credible monitoring systems for human rights-related issues, and the unlikelihood of actual enforcement, many view this as little more than window-dressing.

For governments wanting to see real impact, ‘supply chain due diligence’ regimes pioneered by the EU in relation to timber and conflict minerals present a promising regulatory model.

These regimes seek to curb trade in products derived from, or which aggravate, human rights abuses as well as aiming to promote more responsible sourcing of products by EU importers. They create powerful incentives within partner countries to crack down on harmful practices by producers, which are bolstered further by regulations that demand more proactive human rights risk management by EU operators throughout their supply chains. Capacity-building and aid packages have been deployed to help speed up the necessary reforms.

New regulatory measures imposing mandatory human rights due diligence obligations on companies operating in a much broader range of sectors are now under consideration by the European Commission. While the role of trade-related measures in the enforcement of this new regime is still unclear, trading partners should be sure to preserve the regulatory space for sector-level and company-level initiatives such as these in future agreements.

Understanding the impact of NTPOs on investment

Professor Michael Gasiorek

Increasingly, trade policy is not just all about achieving trade-related outcomes as international trade, by definition, involves interaction with partner countries and therefore trade policy with regard to those partner countries can be used as a means to achieve ‘non-trade policy objectives’ (NTPOs).

In turn this means trade policy is also no longer just about the domestic economy but also about policies and economies in other countries – such as poorer countries achieving sustainable development goals (SDGs), concerns about practices in other countries in areas such as governance or corruption, or a desire to address broader challenges such as climate change.

But the inclusion of NTPOs in trade policy arrangements between countries also creates possible impacts on investment flows between countries. Stronger NTPO commitments could have a negative impact both on foreign direct investment (FDI) and domestic investment because the commitments increase costs for the companies involved which makes the investment less attractive.

However, NTPOs bringing progress on governance, or strengthening institutions, or giving more clarity on environmental regulations could signal a more stable and safe business environment, with production standards which create increased market access for exports – all of which may lead to increased incentives to invest.

A third possibility is that NTPOs do not have much effect either way because, although trade agreement increasingly include provisions on economic and social rights, or civil and political rights, or environmental protection – these are typically ‘best endeavour’ clauses which are frequently not binding or subject to dispute settlement, making them less likely to be implemented.

What are the priorities for the new UK prime minister? Expert comment GBhardwaj 2 September 2022

Experts from across Chatham House examine the range of domestic and foreign policy issues facing Rishi Sunak as he prepares to lead the UK government.

Experts from across Chatham House’s research programmes give their insights on a range of issues facing Rishi Sunak as he becomes UK prime minister, covering energy prices, the climate change agenda, war in Ukraine, China and the Indo-Pacific, Africa, the US, global health, international law and security, science and technology, trade, and the global economic crisis.

Rising energy prices

Antony Froggatt, Senior Research Fellow and Deputy Director, Environment and Society Programme, Chatham House

The social and economic impact of high energy prices this winter may be greater than that of COVID-19. However, in contrast to the pandemic, there has been ample warning of the expected scale of this crisis.

The European Union (EU) gets much more of its energy from Russia than the UK does, but all are part of a largely informal European price zone which is why UK consumers are now facing, what would have been to many, unimaginable bills despite no longer importing energy from Russia.   

The cost of energy will continue to be a major concern for households and businesses and, given the cost of interventions, will significantly affect government finance.

The current policy of capping the unit price for six months increases affordability but will only offer some relief for this winter. The new government urgently needs to look at what happens to bills in the spring and next winter which, from a gas supply perspective, may be even worse than this one.

The EU has reacted with much greater purpose, proposing new legislative packages to diversify supply, accelerate the deployment of renewable energy, make adjustments to markets, and put in place energy saving measures. While these are unlikely to be enough they will make a difference and can become a benchmark for UK policy.

The role that government plays in assisting public and private sectors to save energy will be important. This is where past administrations have wasted the last eight months, where public information campaigns and small technology changes, such as refurbishing and resetting boilers and larger energy consuming products or insulating homes, would have made a difference.

Action needs to be taken across all levels, including co-ordination with the devolved administrations and local government.

Support for new supply needs to be immediately given to new low-carbon technologies which can deliver both cheaply and rapidly, primarily onshore wind and solar, which also help to decarbonize the sector.

The UK will need to maintain, and more likely increase, its relationship with the EU on energy as it continues to trade gas and electricity which is likely to require the resolution of tricky issues such as the Northern Ireland Protocol.

However, the discussions at the European Political Community in early October on greater co-operation on North Sea grids, creating an important opportunity for the accelerated deployment of offshore wind, needs to be taken forward.

Other supply options and market restructuring will be needed and they all must balance affordability, security of supply, and environmental considerations.

The agenda on climate change

Professor Tim Benton, Director, Environment and Society Programme, Chatham House

The record temperatures this summer show how the changing climate is impacting the daily lives of UK citizens. Climate change remains the most important challenge of this century and one that the prime minister will rapidly need to get a grip of ahead of COP27.

Hosting COP26 in 2021, along with Italy, was seen as an important post-Brexit opportunity for the UK in the climate space and ensured the development of many new multilateral sectorial initiatives, such as on climate finance, the Global Methane Pledge and on electric vehicles, while further supporting other emerging initiatives, such as on loss and damage. It will be important for the new prime minister, and the UK’s credibility, to continue to deliver on these.

Concrete things that are needed are a fast roll-out of renewable energy rather than fast-tracking more fossil fuel production, driving ahead the net-zero agenda particularly around land use and food and considering how to restructure markets to better deliver the long-term goals.

Grasping the need to address the demand-side of consumption growth, and not just supply, is key. The UK has prided itself on being a global leader on the climate over the last 15 years but let’s hope that is now not in peril.

Russia and the war in Ukraine

James Nixey, Director, Russia and Eurasia Programme, Chatham House

Supporting Ukraine and confronting Russia are indisputable foreign policy priorities so it is highly likely the new prime minister will look to continue on this path and go with both popular and expert consensus in assisting Ukraine generously and standing up to Russia.

The other question, though, is to what extent the UK’s position can continue to make a difference to the outcome of the war.

Bringing the waverers of western Europe more firmly on board is surely beyond any UK prime minister’s ability considering the UK’s post-Brexit behaviour where the UK still has its own questions to answer including over the failure to tackle the problems of Russian influence at home.

That said, Brexit may not always be relevant to shared hard security challenges. Other countries do see the difference training, money and weapons are making and, if these continue to bring success, it is possible even the waverers can be guilted into providing more aid and economic support.

However, supporting Ukraine is one thing. Truly understanding Russia and devising a coherent Russia strategy is another. What needs to be learned is that Russia, in its present incarnation, cannot be reasoned with whatever the state of the war.

Therefore, given the threat Russia poses to the UK and other democracies, Britain now needs to consider how it can assist with engendering change in Russia. This should not be confused with engineering ‘regime change’ as the Kremlin accuses the UK of doing already.

But it does suggest a more proactive, less defensive Russia policy is required, rather than waiting for the Russian people to instigate change from within. That will take a degree of leadership and political will rarely seen in UK politics.

China and the Indo-Pacific tilt

Ben Bland, Director, Asia-Pacific Programme, Chatham House

Both candidates in the last Conservative leadership contest argued during their campaigns that China was the biggest long-term threat to the UK’s national security. They both promised to call out China’s violations of human rights and international law and extend curbs on China’s access to sensitive technology.

However, to successfully respond to the scale of the challenge, the next prime minister will need to do much more than say what they do not want from Beijing. There needs to be a convincing, positive vision for how the UK can navigate a world where the centre of global economic and geopolitical gravity is moving eastwards.

The Indo-Pacific ‘tilt’ which Liz Truss oversaw as UK foreign secretary was a good start. But tilting isn’t a strategy. So what comes next?

At a time when its in-tray is full of problems closer to home, the UK government needs to sustain enhanced levels of engagement in the Indo-Pacific, particularly in Southeast Asia, while investing at home in the UK’s Asia literacy.

That should include more support for research and education about China as well as the rest of this dynamic region. Labelling China a threat does not make it go away. The UK needs to learn how to live in a world where Chinese power and influence will continue to grow from Asia to Latin America and across the UN and other multilateral organizations.

Investing in the UK’s knowledge of, and relationships in, Asia will also support British businesses as they look for new opportunities in fast-growing but challenging emerging markets such as India, Indonesia, and Vietnam.

The UK’s Middle East policy

Dr Lina Khatib, Director, Middle East and North Africa Programme, Chatham House

The UK government must restore a distinct cabinet position for the Middle East and North Africa and reorient to give Iran’s regional role greater focus.

The Middle East portfolio remains hefty and complex and requires diplomatic engagement to match. No sooner had the UK merged the ministerial Middle East portfolio into the broader one of minister of state for Asia and the Middle East than the war on Ukraine began, directing Western attention to Gulf Arab countries as one potential energy source to offset the loss of Russian oil and gas. Yet Gulf Arab countries are hesitating to fully heed Western calls to increase energy production. 

One key cause is Gulf Arab perceptions that the UK and other Western countries have overlooked their concerns of the threats that Iran poses to their security and political clout.

Despite the UK’s characterization of Iraq as ‘post-conflict’, and of the situation in Syria as a ‘crisis’, recent clashes in Baghdad’s Green Zone and American and Israeli bombing of Iran-linked targets in Syria, as well as recurring attacks by Iran-backed groups on targets in Gulf Cooperation Council (GCC) countries, underline Iran’s role in ongoing instability in the Middle East, which threatens the interests of the UK and its allies in the region.

Although the UK’s Foreign, Commonwealth and Development Office resources have been recently redistributed to further support response to the Russian invasion of Ukraine, the UK can, and must, use existing resources earmarked for the Middle East to engage more effectively.

The two are not wholly distinct: Russia is using Iranian drones to attack Ukraine and Iranian military personnel are active on the ground in Ukraine in aid of the Russian military. Iran and Russia’s ongoing military intervention in Syria paved the way for their cooperation in the invasion of Ukraine.

The UK must restore diplomatic cabinet distribution to give the Middle East the attention it requires, but also revising its approach, putting Iran’s regional and international interventions high on the agenda and in parallel to efforts on the Iran nuclear deal.

The UK sees GCC countries as a potential alternative source of energy to Russian oil and gas specifically and as important trade partners more broadly. UK foreign policy must not compartmentalize its approach to the Middle East.

Diplomatic engagement on Iran’s regional role is a key factor in strengthening trust between the UK and its Middle Eastern allies, including in the GCC, which in turn supports the UK’s economic and security priorities. This means UK policy must approach Iran not just more comprehensively, and coherently, but also as a component of the broader strategy of dealing with the geopolitical and economic threats presented by Russia. 

Africa and the UK

Alex Vines, Director, Africa Programme, Chatham House

Senior UK politicians often claim that Africa is a priority but UK prime ministers and foreign secretaries rarely visit the continent. Boris Johnson attending the Commonwealth Heads of Government Summit in Kigali in August was his first as prime minister where he was accompanied by Liz Truss who was then his foreign secretary.

Despite saying she was an Africa enthusiast as secretary of state for international trade and president of the Board of Trade, Truss had never visited the continent. Her focus was consistently on other parts of the world except for defending the UK’s contested partnership with Rwanda to repatriate to Kigali informal migrants to the UK.

Viewing global politics through the lens of great power rivalry has cast African states as second tier players, disrespecting their agency and prided sovereignty and ignoring the preference of many states to remain non-aligned on issues pertaining to great power competition.

This is a mistake as 25 per cent of the UNGA is comprised of African member states and, of them, 21 are Commonwealth members with Gabon and Togo recently joining. The Russian invasion of Ukraine and intensifying competition with China is a reminder that in this era of sharper geopolitics, Africa increasingly matters for UK’s foreign policy objectives.

The new prime minister will need to review the 2021 Integrated Review, which downplayed much of Africa for UK strategy and advocated a pivot focus to East Africa. The war in Ukraine, coupled with democratic reversals in East Africa and worsening stability in West Africa requires a UK priority rethink. With limited resources to support an expanded UK footprint, sharper focus and defined ambition is important.

Continuity is important too. Since 1989, there have been 21 ministers for Africa, an average tenure of just over 18 months. This is not the time to change the UK’s minister responsible for Africa but it is the moment to make once again that post focused just on sub-Saharan Africa rather than also covering the Caribbean and Latin America too.

The UK-US relationship

Dr Leslie Vinjamuri, Director, US and Americas Programme, Chatham House

As the US approaches its midterm elections, the new prime minister should think carefully about the UK’s response to potential disruption or challenges to the legitimacy of electoral results.

The US faces a period of unpredictable politics with the possibility of significant disruption, upheaval, and the potential for violence. The UK should be careful to differentiate between being independent with respect to partisan politics, which is essential, from being neutral with respect to democracy and especially the integrity of elections.

It would be a mistake for the UK prime minister or the next foreign secretary to be neutral on the question of free and fair elections and the importance of democracy in the US. Boris Johnson’s administration, especially his foreign secretary, was poorly equipped to respond to questions about the outcome of the 2020 presidential elections and prevaricated more than once. 

On foreign policy, a shared interest in supporting Ukraine and strengthening NATO is the current anchor for this partnership, but its historical foundation is both deeper and wider.

The new UK prime minister should demonstrate to the US, and to the world, that Britain is serious about its existing international commitments, especially in the Euro-Atlantic and through NATO, but also with respect to Northern Ireland and Europe.

The UK should deepen its participation in the new European Political Community and seize any opportunity to strengthen mechanisms for security cooperation with Europe. It should aim to restore Britain’s reputation as a nation committed to international, regional and domestic multilateral and legal frameworks.

These measures strengthen Britain’s attractiveness to the US and so lend it greater influence in this essential partnership. Any move to undermine the Northern Ireland protocol should be carefully measured against its wider impacts, not only with Europe, but also with the US.

Continuing Boris Johnson’s policy of restraint, rather than demanding a US-UK trade deal, is wise given the persistence of anti-trade sentiment in the US Congress and the looming US midterm elections.

The prime minister should also do what they can to lend support and work effectively and pragmatically with this US administration. What comes next could be disruptive so now is the time to leverage US power and lock the US into durable commitments that enhance international stability and prosperity.

US president Joe Biden is determined and pragmatic. He will choose the partners that best enable him to deliver his foreign policy priorities. The UK will be both more attractive, and less supplicant, to the US if it has a strong relationship with Europe.

Global health priorities

Robert Yates, Director, Global Health Programme and Executive Director, Centre for Universal Health, Chatham House and Emma Ross, Senior Research Fellow, Global Health Programme. 

Global health has been one of the areas where the UK has historically been seen as punching above its weight due to the magnitude of its financing for global health programmes and its reputation as a leader in global health initiatives.

However, the UK’s standing has taken a significant hit since the start of the pandemic with it demonstrating a lack of solidarity in combatting COVID-19 when it hoarded vaccines and failed to lead the G7 in raising adequate funding for the COVAX facility and blocked attempts to share vaccine technologies with developing countries.

Slashing the international aid budget and deprioritizing global health within its aid strategy has further tarnished the UK’s reputation as a global health leader.

Rebuilding the UK’s hard-earned status as a leading force in global health by at least restoring the level of official development assistance (ODA) for health, if not enhancing it, should be one of the new prime minister’s top priorities.

This should include support for major initiatives such as the Financial Intermediary Fund for Pandemic Prevention, Preparedness and Response (FIF), the Hub for Pandemic and Epidemic Intelligence in Berlin and the vaccine technology transfer hub in Africa.

There is a risk that the ongoing pandemic treaty negotiations will result in a weak instrument of little value. The UK prime minister should prioritize the successful outcome of the negotiations by championing provisions that ensure the treaty makes a meaningful difference in enhancing global health security.

There is a need for workable mechanisms to ensure countries cooperate next time in preventing, preparing for and responding to a pandemic and supporting countries that need extra resources while, another related priority, should be to engage in efforts to reform the International Health Regulations in a way that strengthens global health security.

Championing international law

Rashmin Sagoo, Director, International Law Programme, Chatham House

Compliance with international law is in the best interests of the UK, and the new UK government needs to recognize this.  

The UK wants Russia to comply with the UN Charter and stop its aggressive war against Ukraine. It wants China to recognize the rights of its Uighur citizens, for women to be protected from violence in armed conflict, for compliance with nuclear non-proliferation treaties and  negotiate lucrative international trade agreements. 

These are all excellent aims and they should continue to be pursued. But exhortations to the rest of the world to support the international rules-based order ring hollow if they come from a government which itself does not itself adhere to those rules. 

How the UK conducts itself domestically is a mirror of how it conducts itself internationally. What elected UK officials say and do here matters elsewhere. How we treat the rule of law in this country impacts how others treat it – and us.  

The new prime minister has an opportunity to lead by example by ending the slow but dangerous habitualization of the British public becoming numb to government ‘intentions’ to break international law whether or not such threats are ultimately carried out.

There should also be a full public and parliamentary scrutiny of constitutionally significant proposals, such as the Northern Ireland Protocol bill and reform of the Human Rights Act, rather than fast-track them past a public distracted by the cost-of-living crisis. 

International law is founded upon principles of mutual trust, cooperation, good faith and reciprocity. To be a credible global leader, the UK must put the rule of law, including international law, at the heart of both its foreign and domestic policy. They cannot be disaggregated.   

Strengthening international security

Dr Patricia Lewis, Director, International Security Programme, Chatham House

Security and defence will be high on the agenda for the new UK prime minister. Russia’s war in Ukraine and the potential for sudden, wider escalation remains a serious concern.

Threats of nuclear weapons use, possible false flag ‘dirty bomb’ threats, the continuing attacks on the Zaporizhzhia nuclear power plant threats and veiled references to chemical or biological attacks has demonstrated the willingness of Russia to take enormous risks in regard to threatening Europe as a whole in order to achieve its aims.

If Ukraine’s counter-offensive continues to make gains, then NATO countries will likely be threatened again in this manner. These are not just threats to Ukraine but to NATO states. And, most likely, given the significant role it has played in supporting Ukraine militarily, aimed primarily at the UK.

In the longer term, the UK prime minister needs to review the 2021 Integrated Review of Security, Defence, Development and Foreign Policy. The review came following the decision to increase defence spending and the UK secretary of defence Ben Wallace – continuing in place –has been clear that he has no need to increase his budget further although that may change as the impact of inflation becomes clearer across the board.

The Integrated Review is all about serious investment in the science and technology needed for security and defence in the future. Without such investment the UK will not be able to contribute to international security even in the limited way it can now and certainly not in an ambitious way in decades hence.

There are many long-term security threats that the UK will need to grapple with in addition to Russia’s aggression in Europe, not least of which are China’s rising military capabilities and global ambitions.

In the Arctic and Antarctic, China along with several other major economies, has serious ambitions for exploiting natural resources in terms of minerals, energy, particularly as climate change drives fish stock to the polar seas.

The newly-established AUKUS arrangement which plans to produce a nuclear-powered submarine capability for Australia also provides a mechanism for joint investment by Australia, the UK and the US in science and technologies such as in artificial intelligence (AI) and quantum technology. There are discussions about extending this arrangement to other countries such as Japan and could also include the space sector.    

Meanwhile, at home, in the short-term, there will be increasing calls to end Russia’s war in Ukraine. The prime minister will need to be ahead of that game so that Ukraine is supported and European security is enhanced rather than further stressed.

This will require a new approach to international security – a need that was further highlighted at the end of August in New York with yet another collapse of agreement in the Treaty on the Non-Proliferation of Nuclear Weapons as a result of Russia’s veto.

The UK has long played an important diplomatic role in finding creative solutions for international security and the new prime minister would be well advised to lever that reputation.

Supporting science and technology

Marjorie Buchser, Executive Director, Digital Society Initiative, Chatham House, David Lawrence, Research Fellow, UK in the World Initiative Chatham House and Alex Krasodomski, Head of Innovation Partnerships, Chatham House

In science and technology, the UK currently finds itself in a balancing act between the US and the EU: ideologically attached to the light-touch approach of the US while dependent on the EU as an export market and for supply chains.

While Brexit in theory gives Britain more regulatory freedom, UK companies have often ended up abiding by EU regulations they are unable to shape. The new prime minister should explore forms of regulatory cooperation with the EU that prioritize market access while offering incentives to attract scientists and boost technical innovation.

Beyond transatlantic and European partnerships, it is essential for the UK to foster coalitions with a broader group of like-minded democracies which will be crucial to addressing global technology concerns and countering China’s digital model expansion.

Entrenching the UK as a science and technology ‘superpower’ will require a collaborative approach and involve identifying critical areas where the UK can drive international efforts. For example, the UK should build on its recent successes in the sensitive issues of data flows and digital technical standards as well as encourage investment in open-source security and infrastructure.

Finally, it is essential to unblock the skills and talent pipeline. It is difficult and expensive for high-skilled workers to move to the UK and a key source of labour supply has been lost since leaving the EU. The UK should consider introducing a Commonwealth visa scheme and radically reduce the cost for science and technology companies to offer those visas.

Strengthening infrastructure and housing, particularly in areas that need levelling up, will allow talent to move to areas with the most productive opportunities. 

Trade, climate and green supply chains

Bernice Lee, Research Director, Futures; Hoffmann Distinguished Fellow for Sustainability; Chair, Sustainability Accelerator Advisory Board 

The new prime minister will soon find the answers to the UK’s supply security challenges and soaring energy and food prices as well as future growth lie not at home but are global problems.

At a time of crisis, solutions can only come from countries working together. The UK is a perfectly sized state with plenty of heft but it is not so large as to be able to afford to ignore the needs of others.

It should lead the convening of a growing ‘coalition of the willing’ on trade, climate and green supply chains which could include Australia and Canada as well as developing nations with large extractive sectors in Africa and Asia that are pro-trade, pro-climate, pro-development and pro-growth.

Even though working together on trade and green supply chains can reduce unwanted dependencies, support climate action and help businesses unlock the $26 trillion in market opportunities, many governments have yet to take bold steps due to a fear of disguised protectionism.

Meanwhile, the European Union (EU) carbon border adjustment mechanism (CBAM) is fuelling bitter divides on competitiveness and development concerns.

Trade retaliation is likely and most probably will happen in parallel with legal processes at the WTO. These dynamics mean trade will be underused as an instrument but will create challenging dynamics for COP27. 

Although the Agreement on Climate Change, Trade, and Sustainability (ACCTS) was launched in 2019, the UK could fill a leadership gap since no major economies have positioned themselves as leaders at the intersection of trade, climate, and green supply chains.

British International Investment, the UK’s development institution, should support the establishment and scaling of low-carbon, resource-efficient, sustainable and deforestation-free supply chains which could help fuel the next generation of growth in the UK and beyond.

Improve regulation, give priority to trade relations with the EU, and maintain transparency

Creon Butler, Research Director, Trade, Investment and New Governance Models, and Director, Global Economy and Finance Programme

The UK’s new prime minister comes into office with the country facing the most serious set of economic challenges since 2008-09.

But, in contrast to the global financial crisis, the causes of today’s crisis are more multifaceted and to a degree more UK-specific: the Brexit trade shock; increased public spending pressures linked to the backlog in the NHS and potentially serious long-term effects of ‘long COVID’ and disrupted schooling; the unprecedented shock to energy prices following Russia’s invasion of Ukraine linked in part to the UK’s lack of gas storage capacity; and the shock to market confidence in the UK’s economic management resulting from the 44-day Liz Truss administration.

While the new prime minister should not delay addressing the UK’s long-term challenges, there are three critical questions which will help determine the success or failure of the government’s approach.

First, should the priority be less regulation or, in the context of the tech revolution and the need to accelerate the transformation of the economy to net zero, smarter regulation?

The ICC response to Russia’s war gives hope for justice Expert comment NCapeling 19 March 2023

The ICC’s arrest warrants against Putin and Lvova-Belova show the commission of international crimes is not without consequences.

Warrants of arrest for Russian president Vladimir Putin and Maria Alekseyevna Lvova-Belova, commissioner for children’s rights in the president’s office, have been issued because the Pre-Trial Chamber II of the International Criminal Court (ICC) has reasonable grounds to believe they have committed war crimes.

Following an independent investigation and evidence-gathering by the ICC prosecutor Karim Khan in his first new case since taking office, the pair are accused of committing two different war crimes – the unlawful deportation of children from Ukraine to Russia, and the unlawful transfer of children from occupied areas of Ukraine to the Russian Federation.

The focus on those two war crimes is likely due to clear evidence that deportation and forcible transfer of thousands of Ukrainian children have occurred, as the Russian government was overt about its policy of taking Ukrainian children to Russia and placing them in camps or putting them up for adoption by Russian families.

Furthermore, in line with the Office of the Prosecutor’s policy on children, crimes against children are prioritized given their particularly vulnerable status.

Jurisdiction and enforcement

The ICC does not have jurisdiction over crimes committed fully in Russia by Russian nationals, as Russia is not a party to the Rome Statute which created the ICC.

However, it does have jurisdiction over war crimes, crimes against humanity, and genocide committed in Ukraine irrespective of who committed them, pursuant to two declarations lodged by Ukraine in 2014 accepting the Court’s jurisdiction over its territory from November 2013.

Although a prosecution has been initiated, it is ultimately for the judges of the ICC to decide on the accused’s fate. But the chances of Putin getting arrested or tried for these offences are slim.

The ICC lacks enforcement or police powers and depends on state cooperation to execute arrest warrants. Also, because it cannot try individuals in their absence, a trial or conviction cannot occur without Putin and Lvova-Belova being in custody.

But by issuing and unsealing these arrest warrants, the ICC is relying on the symbolic function of international criminal law – it is publicly naming and shaming Putin and Lvova-Belova for the commission of serious atrocities, and it is sending a message to other leaders and the international community that such actions are not without consequence.

The arrest warrants also give victims some form of vindication or recognition for their suffering and hope for justice in the future. And making the warrants public enables the ICC to reclaim itself as a key avenue for ensuring accountability for international crimes, following a wave of criticism and disenchantment about its work in Africa and delays in advancing its investigation on Afghanistan.

International courts gearing into action

This ICC case is the latest in a series of ongoing cases related to Russia’s war in Ukraine before different international courts and tribunals. Others include at least four cases before the European Court of Human Rights for events that occurred before Russia was excluded from the Council of Europe, such as the MH17 flight case and the annexation of Crimea.

Two cases have also been brought by Ukraine against Russia before the International Court of Justice – in 2017 and 2022 – with hearings scheduled for June. An unprecedented number of states parties have sought to intervene in one or more of these cases.

Each case must be considered on its own merits and the decisions cannot be prejudged. But they showcase an important feature of the global legal system and its judicial architecture that cannot be underestimated – the ability to quickly swing into action in response to violations of international law. In this case, the response was prompted by Russia’s aggression against Ukraine in breach of the United Nations Charter and fundamental principles of international law.

A starting point for a bigger case

The ICC prosecutor already has a broader investigation into other international crimes committed in Ukraine since 21 November 2013. So this is likely to be just the starting point of a much bigger case against Putin and other senior Russian officials for international crimes committed in the context of the war in Ukraine and within the ICC’s jurisdiction.

These potentially include other war crimes such as the indiscriminate or disproportionate targeting of civilians, crimes against humanity, and genocide.

Mammalian circadian clocks are driven by transcription/translation feedback loops composed of positive transcriptional activators (BMAL1 and CLOCK) and negative repressors (CRYPTOCHROMEs (CRYs) and PERIODs (PERs)). CRYs, in complex with PERs, bind to the BMAL1/CLOCK complex and repress E-box–driven transcription of clock-associated genes. There are two individual CRYs, with CRY1 exhibiting higher affinity to the BMAL1/CLOCK complex than CRY2. It is known that this differential binding is regulated by a dynamic serine-rich loop adjacent to the secondary pocket of both CRYs, but the underlying features controlling loop dynamics are not known. Here we report that allosteric regulation of the serine-rich loop is mediated by Arg-293 of CRY1, identified as a rare CRY1 SNP in the Ensembl and 1000 Genomes databases. The p.Arg293His CRY1 variant caused a shortened circadian period in a Cry1−/−Cry2−/− double knockout mouse embryonic fibroblast cell line. Moreover, the variant displayed reduced repressor activity on BMAL1/CLOCK driven transcription, which is explained by reduced affinity to BMAL1/CLOCK in the absence of PER2 compared with CRY1. Molecular dynamics simulations revealed that the p.Arg293His CRY1 variant altered a communication pathway between Arg-293 and the serine loop by reducing its dynamicity. Collectively, this study provides direct evidence that allosterism in CRY1 is critical for the regulation of circadian rhythm.

Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host–pathogen interaction.

CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro. CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1.

Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential.

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