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Seyed Mojtaba Ghiasi, Nicolai Krogh, Björn Tyrberg, Thomas Mandrup-Poulsen
Stress-related changes in β-cell mRNA levels result from a balance between gene transcription and mRNA decay. The regulation of RNA decay pathways has not been investigated in pancreatic β-cells. We found that no-go and nonsense-mediated RNA decay pathway components (RDPC) and exoribonuclease complexes were expressed in INS-1 cells and human islets. Pelo, Dcp2, Dis3L2, Upf2 and Smg1/5/6/7 were up-regulated by inflammatory cytokines in INS-1 cells under conditions where central β-cell mRNAs were down-regulated...
July 31, 2018: Diabetes
Yi-Shiuan Chen, Yi-Hsin Fan, Chih-Feng Tien, Andrew Yueh, Ruey-Yi Chang
Flaviviruses accumulate abundant subgenomic RNA (sfRNA) in infected cells. It has been reported that sfRNA results from stalling of host 5'-to-3' exoribonuclease XRN1 at the highly structured RNA of the 3' untranslated region (UTR). Although XRN1 digestion of a 3'-terminal 800-nt RNA could stall at a position to generate the sfRNA in vitro, we found that knocking out XRN1 had no effect on the accumulation of sfRNA in Japanese encephalitis virus (JEV) infected cells. Mutagenesis studies revealed that the stemloop II (SLII) at the 3' UTR is required for the accumulation of sfRNA...
2018: PloS One
Jens Kretschmer, Harita Rao, Philipp Hackert, Katherine E Sloan, Claudia Höbartner, Markus T Bohnsack
N6-methyladenosine (m6A) modifications in RNAs play important roles in regulating many different aspects of gene expression. While m6As can have direct effects on the structure, maturation or translation of mRNAs, such modifications can also influence the fate of RNAs via proteins termed "readers" that specifically recognise and bind modified nucleotides. Several YTH domain-containing proteins have been identified as m6A readers that regulate the splicing, translation or stability of specific mRNAs...
July 3, 2018: RNA
Sophie Atkinson, Samuel Marguerat, Danny Bitton, Francois Bachand, Maria Rodriguez-Lopez, Charalampos Rallis, Jean-Francois Lemay, Cristina Cotobal, Michal Malecki, Pawel Smialowski, Juan Mata, Philipp Korber, Jurg Bahler
Long non-coding RNAs (lncRNAs), which are longer than 200 nucleotides but often unstable, contribute a substantial and diverse portion to pervasive non-coding transcriptomes. Most lncRNAs are poorly annotated and understood, although several play important roles in gene regulation and diseases. Here we systematically uncover and analyse lncRNAs in Schizosaccharomyces pombe. Based on RNA-seq data from twelve RNA-processing mutants and nine physiological conditions, we identify 5775 novel lncRNAs, nearly 4-times the previously annotated lncRNAs...
June 18, 2018: RNA
Yalena Amador-Cañizares, Annie Bernier, Joyce A Wilson, Selena M Sagan
Hepatitis C virus (HCV) recruits two molecules of the liver-specific microRNA-122 (miR-122) to the 5' end of its genome. This interaction promotes viral RNA accumulation, but the precise mechanism(s) remain incompletely understood. Previous studies suggest that miR-122 is able to protect the HCV genome from 5' exonucleases (Xrn1/2), but this protection is not sufficient to account for the effect of miR-122 on HCV RNA accumulation. Thus, we investigated whether miR-122 was also able to protect the viral genome from innate sensors of RNA or cellular pyrophosphatases...
June 1, 2018: Nucleic Acids Research
Alyssa Flobinus, Nicolas Chevigny, Phillida A Charley, Tanja Seissler, Elodie Klein, Claudine Bleykasten-Grosshans, Claudio Ratti, Salah Bouzoubaa, Jeffrey Wilusz, David Gilmer
The RNA3 species of the beet necrotic yellow vein virus (BNYVV), a multipartite positive-stranded RNA phytovirus, contains the 'core' nucleotide sequence required for its systemic movement in Beta macrocarpa . Within this 'core' sequence resides a conserved "coremin" motif of 20 nucleotides that is absolutely essential for long-distance movement. RNA3 undergoes processing steps to yield a noncoding RNA3 (ncRNA3) possessing "coremin" at its 5' end, a mandatory element for ncRNA3 accumulation...
March 19, 2018: Viruses
Joséphine Zangari, Marius Ilie, Florian Rouaud, Laurie Signetti, Mickaël Ohanna, Robin Didier, Barnabé Roméo, Dana Goldoni, Nicolas Nottet, Cathy Staedel, Jocelyn Gal, Bernard Mari, Baharia Mograbi, Paul Hofman, Patrick Brest
No abstract text is available yet for this article.
April 20, 2018: Nucleic Acids Research
Saijo Thomas, Jiyoti Verma, Megan Woolfit, Scott L O'Neill
Wolbachia is currently being developed as a novel tool to block the transmission of dengue viruses (DENV) by Aedes aegypti. A number of mechanisms have been proposed to explain the DENV-blocking phenotype in mosquitoes, including competition for fatty acids like cholesterol, manipulation of host miRNAs and upregulation of innate immune pathways in the mosquito. We examined the various stages in the DENV infection process to better understand the mechanism of Wolbachia-mediated virus blocking (WMVB). Our results suggest that infection with Wolbachia does not inhibit DENV binding or cell entry, but reduces virus replication...
March 2018: PLoS Pathogens
Elizabeth Delorme-Axford, Emma Abernathy, Nicholas J Lennemann, Amélie Bernard, Aileen Ariosa, Carolyn B Coyne, Karla Kirkegaard, Daniel J Klionsky
Macroautophagy/autophagy is a conserved catabolic process that promotes survival during stress. Autophagic dysfunction is associated with pathologies such as cancer and neurodegenerative diseases. Thus, autophagy must be strictly modulated at multiple levels (transcriptional, post-transcriptional, translational and post-translational) to prevent deregulation. Relatively little is known about the post-transcriptional control of autophagy. Here we report that the exoribonuclease Xrn1/XRN1 functions as a negative autophagy factor in the yeast Saccharomyces cerevisiae and in mammalian cells...
2018: Autophagy
Reed S Sorenson, Malia J Deshotel, Katrina Johnson, Frederick R Adler, Leslie E Sieburth
The decay of mRNA plays a vital role in modulating mRNA abundance, which, in turn, influences cellular and organismal processes. In plants and metazoans, three distinct pathways carry out the decay of most cytoplasmic mRNAs: The mRNA decapping complex, which requires the scaffold protein VARICOSE (VCS), removes a protective 5' cap, allowing for 5' to 3' decay via EXORIBONUCLEASE4 (XRN4, XRN1 in metazoans and yeast), and both the exosome and SUPPRESSOR OF VCS (SOV)/DIS3L2 degrade RNAs in the 3' to 5' direction...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Andrea MacFadden, Zoe O'Donoghue, Patricia A G C Silva, Erich G Chapman, René C Olsthoorn, Mark G Sterken, Gorben P Pijlman, Peter J Bredenbeek, Jeffrey S Kieft
Flaviviruses such as Yellow fever, Dengue, West Nile, and Zika generate disease-linked viral noncoding RNAs called subgenomic flavivirus RNAs. Subgenomic flavivirus RNAs result when the 5'-3' progression of cellular exoribonuclease Xrn1 is blocked by RNA elements called Xrn1-resistant RNAs located within the viral genome's 3'-untranslated region that operate without protein co-factors. Here, we show that Xrn1-resistant RNAs can halt diverse exoribonucleases, revealing a mechanism in which they act as general mechanical blocks that 'brace' against an enzyme's surface, presenting an unfolding problem that confounds further enzyme progression...
January 9, 2018: Nature Communications
Qing Li, Hongdan Yang, Lin He, Qun Wang
Spermatogenesis involves a series of process including exiting from the mitotic cell cycle, entry into meiosis, completion of complex differentiation programs, and producing spermatozoa. Expression of various genes in an ordered manner, and interactions between various genes and their protein products, primarily controlled at the post-transcriptional level with DEAD-box RNA helicases playing a crucial role in germ cell development, are required for production of fertile sperm. Many members of this family have been deeply studied in spermatogenesis, such as DDX3X, DDX25 and DDX4, but few data are available on DDX52...
March 10, 2018: Gene
Takeo Wada, Attila Becskei
The turnover of the RNA molecules is determined by the rates of transcription and RNA degradation. Several methods have been developed to study RNA turnover since the beginnings of molecular biology. Here we summarize the main methods to measure RNA half-life: transcription inhibition, gene control, and metabolic labelling. These methods were used to detect the cellular activity of the mRNAs degradation machinery, including the exo-ribonuclease Xrn1 and the exosome. On the other hand, the study of the differential stability of mature RNAs has been hampered by the fact that different methods have often yielded inconsistent results...
December 15, 2017: International Journal of Molecular Sciences
Phillida A Charley, Carol J Wilusz, Jeffrey Wilusz
Regulated mRNA decay plays a vital role in determining both the level and quality of cellular gene expression. Viral RNAs must successfully evade this host RNA decay machinery to establish a productive infection. One way for RNA viruses to accomplish this is to target the cellular exoribonuclease XRN1, because this enzyme is accessible in the cytoplasm and plays a major role in mRNA decay. Members of the Flaviviridae use RNA structures in their 5'- or 3'-untranslated regions to stall and repress XRN1, effectively stabilizing viral RNAs while also causing significant dysregulation of host cell mRNA stability...
January 5, 2018: Journal of Biological Chemistry
Maxime Wery, Camille Gautier, Marc Descrimes, Mayuko Yoda, Hervé Vennin-Rendos, Valérie Migeot, Daniel Gautheret, Damien Hermand, Antonin Morillon
Antisense transcription can regulate sense gene expression. However, previous annotations of antisense transcription units have been based on detection of mature antisense long noncoding (aslnc)RNAs by RNA-seq and/or microarrays, only giving a partial view of the antisense transcription landscape and incomplete molecular bases for antisense-mediated regulation. Here, we used native elongating transcript sequencing to map genome-wide nascent antisense transcription in fission yeast. Strikingly, antisense transcription was detected for most protein-coding genes, correlating with low sense transcription, especially when overlapping the mRNA start site...
February 2018: RNA
Fumiaki Mori, Kunikazu Tanji, Yasuo Miki, Yasuko Toyoshima, Hidenao Sasaki, Mari Yoshida, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
mRNA turnover controls gene expression under various conditions in aging and neurodegenerative diseases. Polyglutamine (polyQ) diseases and intranuclear inclusion body disease (INIBD) are neurodegenerative diseases characterized by the formation of nuclear inclusions. These inclusions are immunopositive for several proteins associated with amyotrophic lateral sclerosis. In amyotrophic lateral sclerosis, the processing of RNA from gene transcription through degradation (RNA metabolism) has been reported to be altered...
January 1, 2018: Neuroscience Letters
Joseph Russo, Jeffrey Wilusz
In this issue of Molecular Cell, Horvathova et al. (2017) have developed a powerful approach to single-molecule assessment of RNA decay in living cells by exploiting the ability of flavivirus RNA structural elements to trap XRN1 decay intermediates in dual-labeled reporter constructs.
November 2, 2017: Molecular Cell
Clément Charenton, Claudine Gaudon-Plesse, Zaineb Fourati, Valerio Taverniti, Régis Back, Olga Kolesnikova, Bertrand Séraphin, Marc Graille
The Pat1 protein is a central player of eukaryotic mRNA decay that has also been implicated in translational control. It is commonly considered a central platform responsible for the recruitment of several RNA decay factors. We demonstrate here that a yeast-specific C-terminal region from Pat1 interacts with several short motifs, named helical leucine-rich motifs (HLMs), spread in the long C-terminal region of yeast Dcp2 decapping enzyme. Structures of Pat1-HLM complexes reveal the basis for HLM recognition by Pat1...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
Magdalena Natalia Wojtas, Radha Raman Pandey, Mateusz Mendel, David Homolka, Ravi Sachidanandam, Ramesh S Pillai
N6 -methyladenosine (m6 A) is an essential internal RNA modification that is critical for gene expression control in most organisms. Proteins with a YTH domain recognize m6 A marks and are mediators of molecular functions like RNA splicing, mRNA decay, and translation control. Here we demonstrate that YTH domain-containing 2 (YTHDC2) is an m6 A reader that is essential for male and female fertility in mice. High-throughput mapping of the m6 A transcriptome and expression analysis in the Yhtdc2 mutant testes reveal an upregulation of m6 A-enriched transcripts...
October 19, 2017: Molecular Cell
Jun Cheng, Kerstin C Maier, Žiga Avsec, Petra Rus, Julien Gagneur
The stability of mRNA is one of the major determinants of gene expression. Although a wealth of sequence elements regulating mRNA stability has been described, their quantitative contributions to half-life are unknown. Here, we built a quantitative model for Saccharomyces cerevisiae based on functional mRNA sequence features that explains 59% of the half-life variation between genes and predicts half-life at a median relative error of 30%. The model revealed a new destabilizing 3' UTR motif, ATATTC, which we functionally validated...
November 2017: RNA
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