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Correlations of Long Noncoding RNA HNF4A-AS1 Alternative Transcripts with Liver Diseases and Drug Metabolism [Articles]

Hepatocyte nuclear factor 4 alpha antisense 1 (HNF4A-AS1) is a long noncoding RNA (lncRNA) gene physically located next to the transcription factor HNF4A gene in the human genome. Its transcription products have been reported to inhibit the progression of hepatocellular carcinoma (HCC) and negatively regulate the expression of cytochrome P450s (CYPs), including CYP1A2, 2B6, 2C9, 2C19, 2E1, and 3A4. By altering CYP expression, lncRNA HNF4A-AS1 also contributes to the susceptibility of drug-induced liver injury. Thus, HNF4A-AS1 lncRNA is a promising target for controlling HCC and modulating drug metabolism. However, HNF4A-AS1 has four annotated alternative transcripts in the human genome browsers, and it is unclear which transcripts the small interfering RNAs or small hairpin RNAs used in the previous studies are silenced and which transcripts should be used as the target. In this study, four annotated and two newly identified transcripts were confirmed. These six transcripts showed different expression levels in different liver disease conditions, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and obesity. The expression patterns of all HNF4A-AS1 transcripts were further investigated in liver cell growth from human embryonic stem cells to matured hepatocyte-like cells, HepaRG differentiation, and exposure to rifampicin treatment. Several HNF4A-AS1 transcripts highly displayed correlations with these situations. In addition, some of the HNF4A-AS1 transcripts also showed a strong correlation with CYP3A4 during HepaRG maturation and rifampicin exposure. Our findings provide valuable insights into the specific roles of HNF4A-AS1 transcripts, paving the way for more targeted therapeutic strategies for liver diseases and drug metabolism.

SIGNIFICANCE STATEMENT

This study explores the alternative transcripts of HNF4A-AS1, showing how their expression changes in different biological conditions, from various liver diseases to the growth and differentiation of hepatocytes and drug metabolism. The generated knowledge is essential for understanding the independent roles of different transcripts from the same lncRNA in different liver diseases and drug metabolism situations.




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LIN28A binds to meiotic gene transcripts and modulates translation in male germ cells [RESEARCH ARTICLE]

Mei Wang, Luping Yu, Shu Wang, Fan Yang, Min Wang, Lufan Li, and Xin Wu

RNA-binding protein LIN28A is required for maintaining tissue homeostasis, including the reproductive system, but the underlying mechanisms on how LIN28A regulates germline progenitors remain unclear. Here, we dissected LIN28A-binding targets using high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) in the mouse testes. LIN28A preferentially binds to CDS or 3'UTR regions through these sites with GGAG(A) sequences enriched within mRNAs. Further investigation of Lin28a null mouse testes indicated that meiosis-associated mRNAs mediated by LIN28A were differentially expressed. Next, ribosome profiling revealed that the mRNA levels of these targets were significantly reduced in polysome fractions, and their protein expression levels decreased in the Lin28a null mouse testes, even when meiotic arrest in null mouse testes was not apparent. Collectively, these findings provide a set of binding targets that are regulated by LIN28A, which may potentially be the mechanism for the prominent role of LIN28A in regulating mammalian undifferentiated spermatogonia fates and male fertility.




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Karpel Solutions Partners with Net Transcripts, a VIQ Solutions Company, to Simplify Workflow for Criminal Case Documentation

The integration within PROSECUTORbyKarpel (PbK) and DEFENDERbyKarpel (DbK) enables legal professionals to streamline their transcript processes




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The Elston Report: Secret chat group transcripts revealed

Sir Howard Elston, our community affairs editor, lifts the lid on local social media groups.




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Russia Investigation Transcripts and Documents | Permanent Select Committee on Intelligence




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‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion

The following article, ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion, was first published on 100PercentFedUp.com.

Transcripts of House Intelligence Committee interviews have been cleared for release, and Adam Schiff is reportedly in panic mode. Unfortunately for Schiff, top law enforcement and intel officials said they saw no evidence of collusion between the Trump campaign and Russia in the transcripts. Republicans sought and got approval for the release of the transcripts […]

Continue reading: ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion ...




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The full transcripts of the Second Series of Regional Real-time Online Conferences on Risk Assessment and Risk Management (February 2010).




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Indiana Using Data to Build Better Transcripts, College Transitions

Indiana's efforts to give students more control over their academic transcripts may prove a boon for researchers and school reformers, too.




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Russia probe transcripts released by House Intelligence Committee

Reaction and analysis from Fox News contributor Byron York and former Florida Attorney General Pam Bondi.





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The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

ABSTRACT

The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant’s vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor.

IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.




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Transcripts Reveal the Lies of Schiff & Dems on Russia

The Trump-Russia collusion investigation was an elaborate and intentional hoax, staged by the most unscrupulous and power-mad political operatives this country has ever seen.




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Political Takeaways From the Federal Reserve Transcripts


The Federal Reserve last week released transcripts of Federal Open Market Committee (FOMC) meetings that took place in 2008 amidst a worsening global financial crisis. Sarah Binder describes what was found amongst the transcripts. Alongside financial and economic crises facing the Fed that year, the Fed faced a crisis as a political institution.  

      
 
 




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If you want transcripts of Donald Trump's calls to Vladimir Putin you'll have to ask us: Kremlin

Asked about Democrats' push for the publication of Putin-Trump calls, Kremlin spokesman Dmitry Peskov responded that 'the publication is possible only on mutual accord.'




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Declassified transcripts show Obama officials could not provide evidence of Russia-Trump collusion

The transcripts - which were released Thursday - come from 57 witnesses who were interviewed by the committee during the Trump Russia probe.




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Real-time quantification of fusion transcripts with ligase chain reaction by direct ligation of adjacent DNA probes at fusion junction

Analyst, 2020, Advance Article
DOI: 10.1039/D0AN00163E, Paper
Fengxia Su, Jianing Ji, Pengbo Zhang, Fangfang Wang, Zhengping Li
A fusion transcript assay is developed based on direct ligation and ligase chain reaction.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry




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Phase separation driven by production of architectural RNA transcripts

Soft Matter, 2020, Accepted Manuscript
DOI: 10.1039/C9SM02458A, Paper
Tetsuya Yamamoto, Tomohiro Yamazaki, Tetsuro Hirose
We here use an extension of the Flory-Huggins theory to predict that the phase separation is driven by the production of architectural RNA (arcRNA) at a DNA locus with a...
The content of this RSS Feed (c) The Royal Society of Chemistry




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The governor and the king : irony, hidden transcripts, and negotiating empire in the Fourth Gospel / Arthur M. Wright Jr. ; foreword by Frances Taylor Gench

Wright, Arthur M., author