pncRNA-D is an irradiation-induced 602-nt long noncoding RNA transcribed from the promoter region of the cyclin D1 (CCND1) gene. CCND1 expression is predicted to be inhibited through an interplay between pncRNA-D and RNA-binding protein TLS/FUS. Because the pncRNA-D–TLS interaction is essential for pncRNA-D–stimulated CCND1 inhibition, here we studied the possible role of RNA modification in this interaction in HeLa cells. We found that osmotic stress induces pncRNA-D by recruiting RNA polymerase II to its promoter. pncRNA-D was highly m6A-methylated in control cells, but osmotic stress reduced the methylation and also arginine methylation of TLS in the nucleus. Knockdown of the m6A modification enzyme methyltransferase-like 3 (METTL3) prolonged the half-life of pncRNA-D, and among the known m6A recognition proteins, YTH domain-containing 1 (YTHDC1) was responsible for binding m6A of pncRNA-D. Knockdown of METTL3 or YTHDC1 also enhanced the interaction of pncRNA-D with TLS, and results from RNA pulldown assays implicated YTHDC1 in the inhibitory effect on the TLS–pncRNA-D interaction. CRISPR/Cas9-mediated deletion of candidate m6A site decreased the m6A level in pncRNA-D and altered its interaction with the RNA-binding proteins. Of note, a reduction in the m6A modification arrested the cell cycle at the G0/G1 phase, and pncRNA-D knockdown partially reversed this arrest. Moreover, pncRNA-D induction in HeLa cells significantly suppressed cell growth. Collectively, these findings suggest that m6A modification of the long noncoding RNA pncRNA-D plays a role in the regulation of CCND1 gene expression and cell cycle progression.

tRNAs universally carry a CCA nucleotide triplet at their 3'-ends. In eukaryotes, the CCA is added post-transcriptionally by the CCA-adding enzyme (CAE). The mitochondrion of the parasitic protozoan Trypanosoma brucei lacks tRNA genes and therefore imports all of its tRNAs from the cytosol. This has generated interest in the tRNA modifications and their distribution in this organism, including how CCA is added to tRNAs. Here, using a BLAST search for genes encoding putative CAE proteins in T. brucei, we identified a single ORF, Tb927.9.8780, as a potential candidate. Knockdown of this putative protein, termed TbCAE, resulted in the accumulation of truncated tRNAs, abolished translation, and inhibited both total and mitochondrial CCA-adding activities, indicating that TbCAE is located both in the cytosol and mitochondrion. However, mitochondrially localized tRNAs were much less affected by the TbCAE ablation than the other tRNAs. Complementation assays revealed that the N-terminal 10 amino acids of TbCAE are dispensable for its activity and mitochondrial localization and that deletion of 10 further amino acids abolishes both. A growth arrest caused by the TbCAE knockdown was rescued by the expression of the cytosolic isoform of yeast CAE, even though it was not imported into mitochondria. This finding indicated that the yeast enzyme complements the essential function of TbCAE by adding CCA to the primary tRNA transcripts. Of note, ablation of the mitochondrial TbCAE activity, which likely has a repair function, only marginally affected growth.

The ribosome biogenesis factor Las1 is an essential endoribonuclease that is well-conserved across eukaryotes and a newly established member of the higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain-containing nuclease family. HEPN nucleases participate in diverse RNA cleavage pathways and share a short HEPN nuclease motif (RφXXXH) important for RNA cleavage. Most HEPN nucleases participate in stress-activated RNA cleavage pathways; Las1 plays a fundamental role in processing pre-rRNA. Underscoring the significance of Las1 function in the cell, mutations in the human LAS1L (LAS1-like) gene have been associated with neurological dysfunction. Two juxtaposed HEPN nuclease motifs create Las1's composite nuclease active site, but the roles of the individual HEPN motif residues are poorly defined. Here using a combination of in vivo experiments in Saccharomyces cerevisiae and in vitro assays, we show that both HEPN nuclease motifs are required for Las1 nuclease activity and fidelity. Through in-depth sequence analysis and systematic mutagenesis, we determined the consensus HEPN motif in the Las1 subfamily and uncovered its canonical and specialized elements. Using reconstituted Las1 HEPN-HEPN' chimeras, we defined the molecular requirements for RNA cleavage. Intriguingly, both copies of the Las1 HEPN motif were important for nuclease function, revealing that both HEPN motifs participate in coordinating the RNA within the Las1 active site. We also established that conformational flexibility of the two HEPN domains is important for proper nuclease function. The results of our work reveal critical information about how dual HEPN domains come together to drive Las1-mediated RNA cleavage.

Site-specific arrest of RNA polymerases (RNAPs) is fundamental to several technologies that assess RNA structure and function. Current in vitro transcription “roadblocking” approaches inhibit transcription elongation by blocking RNAP with a protein bound to the DNA template. One limitation of protein-mediated transcription roadblocking is that it requires inclusion of a protein factor extrinsic to the minimal in vitro transcription reaction. In this work, we developed a chemical approach for halting transcription by Escherichia coli RNAP. We first established a sequence-independent method for site-specific incorporation of chemical lesions into dsDNA templates by sequential PCR and translesion synthesis. We then show that interrupting the transcribed DNA strand with an internal desthiobiotin-triethylene glycol modification or 1,N6-etheno-2'-deoxyadenosine base efficiently and stably halts Escherichia coli RNAP transcription. By encoding an intrinsic stall site within the template DNA, our chemical transcription roadblocking approach enables display of nascent RNA molecules from RNAP in a minimal in vitro transcription reaction.

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.

Kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are two major, closely related receptor subtypes in the glutamate ion channel family. Excessive activities of these receptors have been implicated in a number of central nervous system diseases. Designing potent and selective antagonists of these receptors, especially of kainate receptors, is useful for developing potential treatment strategies for these neurological diseases. Here, we report on two RNA aptamers designed to individually inhibit kainate and AMPA receptors. To improve the biostability of these aptamers, we also chemically modified these aptamers by substituting their 2'-OH group with 2'-fluorine. These 2'-fluoro aptamers, FB9s-b and FB9s-r, were markedly resistant to RNase-catalyzed degradation, with a half-life of ∼5 days in rat cerebrospinal fluid or serum-containing medium. Furthermore, FB9s-r blocked AMPA receptor activity. Aptamer FB9s-b selectively inhibited GluK1 and GluK2 kainate receptor subunits, and also GluK1/GluK5 and GluK2/GluK5 heteromeric kainate receptors with equal potency. This inhibitory profile makes FB9s-b a powerful template for developing tool molecules and drug candidates for treatment of neurological diseases involving excessive activities of the GluK1 and GluK2 subunits.

V. V. Vlasov and N. A. Rautian
Trans. Moscow Math. Soc. 80 (2020), 169-188.
Abstract, references and article information

Researchers have poked another small hole in air gapped security by showing how the electronics inside computer power supply units (PSUs) can be turned into covert data transmission devices.

1 November 2019

The 'Security and Prosperity in Asia' conference looked at the impact of international law in the Asia-Pacific with a focus on regional economic and security issues such as the South China Sea disputes.

Invitation Only Research Event

17 January 2020

Invitation Only Research Event

Event participants

Dr Robin Niblett CMG, Director, Chatham House  
Toshiro Mutoh, Honorary Chairman, Daiwa Institute of Research; CEO, Tokyo Organising Committee of the Olympic and Paralympic Game
José Manuel Barroso, Senior Adviser, Chatham House; President of the European Commission (2004-14); Prime Minister of Portugal (2002-04)
Akihiko Tanaka, President, National Graduate Institute for Policy Studies

18 February 2020

The colored "strings" you see represent air flow around the soccer ball, with the dark blue streams behind the ball signifying a low-pressure wake. Computational fluid dynamics and wind tunnel experiments have shown that there is a transition point between smooth and turbulent flow at around 30 mph, which can dramatically change the path of a kick approaching the net as its speed decreases through the transition point. Players taking free-kicks need not be mathematicians to score, but knowing the results obtained from mathematical facts can help players devise better strategies. The behavior of a ball depends on its surface design as well as on how it.s kicked. Topology, algebra, and geometry are all important to determine suitable shapes, and modeling helps determine desirable ones. The researchers studying soccer ball trajectories incorporate into their mathematical models not only the pattern of a new ball, but also details right down to the seams. Recently there was a radical change from the long-used pentagon-hexagon pattern to the adidas +TeamgeistTM. Yet the overall framework for the design process remains the same: to approximate a sphere, within less than two percent, using two-dimensional panels.

Mathematics contributes in many ways to the process of converting wind power into usable energy. Large-scale weather models are used to find suitable locations for wind farms, while more narrowly focused models incorporating interactions arising from factors such as wake effects and turbulence specify how to situate individual turbines within a farm. In addition, computational fluid dynamics describes air flow and drag around turbines. This helps determine the optimal shapes for the blades, both structurally and aerodynamically, to extract as much energy as possible, and keep noise levels and costs down. Mathematics also helps answer two fundamental questions about wind turbines. First, why three blades? Turbines with fewer blades extract less energy and are noisier (because the blades must turn faster). Those with more than three blades would capture more energy but only about three percent more, which doesn.t justify the increased cost. Second, what percentage of wind energy can a turbine extract? Calculus and laws of conservation provide the justification for Betz Law, which states that no wind turbine can capture more than 60% of the energy in the wind. Modern turbines generally gather 40-50%. So the answer to someone who touts a turbine that can capture 65% of wind energy is "All Betz" are off. For More Information: Wind Energy Explained: Theory, Design and Application, Manwell, McGowan, and Rogers, 2010.

Researcher: Michel C. Molinkovitch, University of Geneva Description: Michel C. Milinkovitch used math, physics, and biology for an amazing discovery about the patterns on a lizard's skin.

Consolidated sales of EUR 146.7 million EBITDA (before IFRS 16) increased strongly by EUR 3.8 million to EUR 2.1 million Forecast for 2019 as a whole confirmed Working capital ratio declines by 2 percentage points to 10.6% euromicron AG, a medium-sized technology group and specialist for the digital networking of business and production processes, published its preliminary figures for the first half of 2019 today.

ssm euromicron GmbH, a system house subsidiary of euromicron AG, is involved in a project to provide the technical equipment for the new building for the Institute of Geosciences at Kiel’s Christian Albrechts University. The seven-story new building is part of a campus-wide modernization initiative that is one of the largest public high-rise projects in the federal state of Schleswig-Holstein.

THERE'S nothing like the sweet taste of victory, especially when it's long in coming.

GIVEN the financial position of the Jamaica Football Federation (JFF), John Barnes had resigned

Jiuzhaigou National Nature Reserve is one of China's most popular tourist attractions, drawing more than five million visitors per year to the sparsely populated mountains of north-western Sichuan. The reserve has been home to farmer-herders for thousands of years, but to conserve the biodiversity and scenic quality of the reserve, park policies prohibit residents from farming, herding and wood cutting.

Global action is also a matter of self-interest for developed economies.

What happens when a service you shared your personal data with is acquired by a giant corporation?