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RNA decay exosome

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https://www.readbyqxmd.com/read/29906447/helicase-dependent-rna-decay-illuminated-by-a-cryo-em-structure-of-a-human-nuclear-rna-exosome-mtr4-complex
#1
Eva-Maria Weick, M Rhyan Puno, Kurt Januszyk, John C Zinder, Michael A DiMattia, Christopher D Lima
The ribonucleolytic RNA exosome interacts with RNA helicases to degrade RNA. To understand how the 3' to 5' Mtr4 helicase engages RNA and the nuclear exosome, we reconstituted 14-subunit Mtr4-containing RNA exosomes from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and human and show that they unwind structured substrates to promote degradation. We loaded a human exosome with an optimized DNA-RNA chimera that stalls MTR4 during unwinding and determined its structure to an overall resolution of 3.45 Å by cryoelectron microscopy (cryo-EM)...
June 14, 2018: Cell
https://www.readbyqxmd.com/read/29880601/diminished-nuclear-rna-decay-upon-salmonella-infection-upregulates-antibacterial-noncoding-rnas
#2
Katsutoshi Imamura, Akiko Takaya, Yo-Ichi Ishida, Yayoi Fukuoka, Toshiki Taya, Ryo Nakaki, Miho Kakeda, Naoto Imamachi, Aiko Sato, Toshimichi Yamada, Rena Onoguchi-Mizutani, Gen Akizuki, Tanzina Tanu, Kazuyuki Tao, Sotaro Miyao, Yutaka Suzuki, Masami Nagahama, Tomoko Yamamoto, Torben Heick Jensen, Nobuyoshi Akimitsu
Cytoplasmic mRNA degradation controls gene expression to help eliminate pathogens during infection. However, it has remained unclear whether such regulation also extends to nuclear RNA decay. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) such as NEAT1v2, are stabilized upon Salmonella infection in HeLa cells. In uninfected cells, the RNA exosome, aided by the Nuclear EXosome Targeting (NEXT) complex, degrades these labile transcripts. Upon infection, the levels of the exosome/NEXT components, RRP6 and MTR4, dramatically decrease, resulting in transcript stabilization...
June 7, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29481617/turnover-of-aberrant-pre-40s-pre-ribosomal-particles-is-initiated-by-a-novel-endonucleolytic-decay-pathway
#3
Elodie Choque, Claudia Schneider, Olivier Gadal, Christophe Dez
Ribosome biogenesis requires more than 200 trans-acting factors to achieve the correct production of the two mature ribosomal subunits. Here, we have identified Efg1 as a novel, nucleolar ribosome biogenesis factor in Saccharomyces cerevisiae that is directly linked to the surveillance of pre-40S particles. Depletion of Efg1 impairs early pre-rRNA processing, leading to a strong decrease in 18S rRNA and 40S subunit levels and an accumulation of the aberrant 23S rRNA. Using Efg1 as bait, we revealed a novel degradation pathway of the 23S rRNA...
February 22, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29415469/circsmarca5-inhibits-migration-of-glioblastoma-multiforme-cells-by-regulating-a-molecular-axis-involving-splicing-factors-srsf1-srsf3-ptb
#4
Davide Barbagallo, Angela Caponnetto, Matilde Cirnigliaro, Duilia Brex, Cristina Barbagallo, Floriana D'Angeli, Antonio Morrone, Rosario Caltabiano, Giuseppe Maria Barbagallo, Marco Ragusa, Cinzia Di Pietro, Thomas Birkballe Hansen, Michele Purrello
Circular RNAs (circRNAs) have recently emerged as a new class of RNAs, highly enriched in the brain and very stable within cells, exosomes and body fluids. To analyze their involvement in glioblastoma multiforme (GBM) pathogenesis, we assayed the expression of twelve circRNAs, physiologically enriched in several regions of the brain, through real-time PCR in a cohort of fifty-six GBM patient biopsies and seven normal brain parenchymas. We focused on hsa_circ_0001445 (circSMARCA5): it was significantly downregulated in GBM biopsies as compared to normal brain tissues ( p -value < 0...
February 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29386391/-arabidopsis-mrna-decay-landscape-arises-from-specialized-rna-decay-substrates-decapping-mediated-feedback-and-redundancy
#5
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
https://www.readbyqxmd.com/read/29351962/rna-helicases-in-rna-decay
#6
REVIEW
Vanessa Khemici, Patrick Linder
RNA molecules have the tendency to fold into complex structures or to associate with complementary RNAs that exoribonucleases have difficulties processing or degrading. Therefore, degradosomes in bacteria and organelles as well as exosomes in eukaryotes have teamed-up with RNA helicases. Whereas bacterial degradosomes are associated with RNA helicases from the DEAD-box family, the exosomes and mitochondrial degradosome use the help of Ski2-like and Suv3 RNA helicases.
February 19, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29298432/characterizing-zc3h18-a-multi-domain-protein-at-the-interface-of-rna-production-and-destruction-decisions
#7
Kinga Winczura, Manfred Schmid, Claudia Iasillo, Kelly R Molloy, Lea Mørch Harder, Jens S Andersen, John LaCava, Torben Heick Jensen
Nuclear RNA metabolism is influenced by protein complexes connecting to both RNA-productive and -destructive pathways. The ZC3H18 protein binds the cap-binding complex (CBC), universally present on capped RNAs, while also associating with the nuclear exosome targeting (NEXT) complex, linking to RNA decay. To dissect ZC3H18 function, we conducted interaction screening and mutagenesis of the protein, which revealed a phosphorylation-dependent isoform. Surprisingly, the modified region of ZC3H18 associates with core histone proteins...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/28973446/ars2-is-a-general-suppressor-of-pervasive-transcription
#8
Claudia Iasillo, Manfred Schmid, Yousra Yahia, Muhammad A Maqbool, Nicolas Descostes, Evdoxia Karadoulama, Edouard Bertrand, Jean-Christophe Andrau, Torben Heick Jensen
Termination of transcription is important for establishing gene punctuation marks. It is also critical for suppressing many of the pervasive transcription events occurring throughout eukaryotic genomes and coupling their RNA products to efficient decay. In human cells, the ARS2 protein has been implicated in such function as its depletion causes transcriptional read-through of selected gene terminators and because it physically interacts with the ribonucleolytic nuclear RNA exosome. Here, we study the role of ARS2 on transcription and RNA metabolism genome wide...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28877463/mpp6-incorporation-in-the-nuclear-exosome-contributes-to-rna-channeling-through-the-mtr4-helicase
#9
Sebastian Falk, Fabien Bonneau, Judith Ebert, Alexander Kögel, Elena Conti
The RNA-degrading exosome mediates the processing and decay of many cellular transcripts. In the yeast nucleus, the ubiquitous 10-subunit exosome core complex (Exo-9-Rrp44) functions with four conserved cofactors (Rrp6, Rrp47, Mtr4, and Mpp6). Biochemical and structural studies to date have shed insights into the mechanisms of the exosome core and its nuclear cofactors, with the exception of Mpp6. We report the 3.2-Å resolution crystal structure of a S. cerevisiae Exo-9-Mpp6 complex, revealing how linear motifs in the Mpp6 middle domain bind Rrp40 via evolutionary conserved residues...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28742025/structure-and-reconstitution-of-yeast-mpp6-nuclear-exosome-complexes-reveals-that-mpp6-stimulates-rna-decay-and-recruits-the-mtr4-helicase
#10
Elizabeth V Wasmuth, John C Zinder, Dimitrios Zattas, Mom Das, Christopher D Lima
Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if these cofactors work together. Using biochemistry with Saccharomyces cerevisiae proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay, albeit with unique dependencies on elements within the nuclear exosome...
July 25, 2017: ELife
https://www.readbyqxmd.com/read/28642780/rrp42-a-subunit-of-exosome-plays-an-important-role-in-female-gametophytes-development-and-mesophyll-cell-morphogenesis-in-arabidopsis
#11
Xiaoyuan Yan, Zongyun Yan, Yuzhen Han
The exosome complex plays a central and essential role in RNA metabolism. However, current research on functions of exosome subunit in plants is limited. Here, we used an egg cell-specific promoter-controlled CRISPR/Cas9 system to knock out RRP42 which encodes a core subunit of the Arabidopsis exosome and presented evidence that RRP42 is essential for the development of female gametophytes. Next, we designed three different amiRNAs targeting RRP42. The rrp42 knock-down mutants mainly displayed variegated and serrated leaves, especially in cauline leaves...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28190770/nuclear-rna-decay-pathways-aid-rapid-remodeling-of-gene-expression-in-yeast
#12
Stefan Bresson, Alex Tuck, Desislava Staneva, David Tollervey
In budding yeast, the nuclear RNA surveillance system is active on all pre-mRNA transcripts and modulated by nutrient availability. To test the role of nuclear surveillance in reprogramming gene expression, we identified transcriptome-wide binding sites for RNA polymerase II and the exosome cofactors Mtr4 (TRAMP complex) and Nab3 (NNS complex) by UV crosslinking immediately following glucose withdrawal (0, 4, and 8 min). In glucose, mRNA binding by Nab3 and Mtr4 was mainly restricted to promoter-proximal sites, reflecting early transcription termination...
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28054965/attacked-from-all-sides-rna-decay-in-antiviral-defense
#13
REVIEW
Jerome M Molleston, Sara Cherry
The innate immune system has evolved a number of sensors that recognize viral RNA (vRNA) to restrict infection, yet the full spectrum of host-encoded RNA binding proteins that target these foreign RNAs is still unknown. The RNA decay machinery, which uses exonucleases to degrade aberrant RNAs largely from the 5' or 3' end, is increasingly recognized as playing an important role in antiviral defense. The 5' degradation pathway can directly target viral messenger RNA (mRNA) for degradation, as well as indirectly attenuate replication by limiting specific pools of endogenous RNAs...
January 4, 2017: Viruses
https://www.readbyqxmd.com/read/27980209/the-cryo-em-structure-of-a-ribosome-ski2-ski3-ski8-helicase-complex
#14
Christian Schmidt, Eva Kowalinski, Vivekanandan Shanmuganathan, Quentin Defenouillère, Katharina Braunger, André Heuer, Markus Pech, Abdelkader Namane, Otto Berninghausen, Micheline Fromont-Racine, Alain Jacquier, Elena Conti, Thomas Becker, Roland Beckmann
Ski2-Ski3-Ski8 (Ski) is a helicase complex functioning with the RNA-degrading exosome to mediate the 3'-5' messenger RNA (mRNA) decay in turnover and quality-control pathways. We report that the Ski complex directly associates with 80S ribosomes presenting a short mRNA 3' overhang. We determined the structure of an endogenous ribosome-Ski complex using cryo-electron microscopy (EM) with a local resolution of the Ski complex ranging from 4 angstroms (Å) in the core to about 10 Å for intrinsically flexible regions...
December 16, 2016: Science
https://www.readbyqxmd.com/read/27871484/identification-of-a-nuclear-exosome-decay-pathway-for-processed-transcripts
#15
Nicola Meola, Michal Domanski, Evdoxia Karadoulama, Yun Chen, Coline Gentil, Dennis Pultz, Kristoffer Vitting-Seerup, Søren Lykke-Andersen, Jens S Andersen, Albin Sandelin, Torben Heick Jensen
The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its co-factor Mtr4p/hMTR4, which links to RNA-binding protein adaptors. One example is the trimeric human nuclear exosome targeting (NEXT) complex, which is composed of hMTR4, the Zn-finger protein ZCCHC8, and the RNA-binding factor RBM7. NEXT primarily targets early and unprocessed transcripts, which demands a rationale for how the nuclear exosome recognizes processed RNAs. Here, we describe the poly(A) tail exosome targeting (PAXT) connection, which comprises the ZFC3H1 Zn-knuckle protein as a central link between hMTR4 and the nuclear poly(A)-binding protein PABPN1...
November 3, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27758893/genome-wide-mapping-of-uncapped-and-cleaved-transcripts-reveals-a-role-for-the-nuclear-mrna-cap-binding-complex-in-cotranslational-rna-decay-in-arabidopsis
#16
Xiang Yu, Matthew R Willmann, Stephen J Anderson, Brian D Gregory
RNA turnover is necessary for controlling proper mRNA levels posttranscriptionally. In general, RNA degradation is via exoribonucleases that degrade RNA either from the 5' end to the 3' end, such as XRN4, or in the opposite direction by the multisubunit exosome complex. Here, we use genome-wide mapping of uncapped and cleaved transcripts to reveal the global landscape of cotranslational mRNA decay in the Arabidopsis thaliana transcriptome. We found that this process leaves a clear three nucleotide periodicity in open reading frames...
October 2016: Plant Cell
https://www.readbyqxmd.com/read/27723196/rna-decay-systems-enhance-reciprocal-switching-of-sense-and-antisense-transcripts-in-response-to-glucose-starvation
#17
Atsuko Miki, Josephine Galipon, Satoshi Sawai, Toshifumi Inada, Kunihiro Ohta
Antisense RNA has emerged as a crucial regulator of opposite-strand protein-coding genes in the long noncoding RNA (lncRNA) category, but little is known about their dynamics and decay process in the context of a stress response. Antisense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation. Here, we investigate the localization and decay of antisense RNAs at fbp1 and other loci, and propose a model to explain the rapid switch between antisense and sense mlonRNA/mRNA transcription triggered by glucose starvation...
December 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/27599263/tmv-induces-rna-decay-pathways-to-modulate-gene-silencing-and-disease-symptoms
#18
Gabriela Conti, Diego Zavallo, Andrea L Venturuzzi, Maria C Rodriguez, Martin Crespi, Sebastian Asurmendi
RNA decay pathways comprise a combination of RNA degradation mechanisms that are implicated in gene expression, development and defense responses in eukaryotes. These mechanisms are known as the RNA Quality Control or RQC pathways. In plants, another important RNA degradation mechanism is the post-transcriptional gene silencing (PTGS) mediated by small RNAs (siRNAs). Notably, the RQC pathway antagonizes PTGS by preventing the entry of dysfunctional mRNAs into the silencing pathway to avoid global degradation of mRNA by siRNAs...
January 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27580880/functional-characterization-of-a-chr13q22-1-pancreatic-cancer-risk-locus-reveals-long-range-interaction-and-allele-specific-effects-on-dis3-expression
#19
Jason W Hoskins, Abdisamad Ibrahim, Mickey A Emmanuel, Sarah M Manmiller, Yinglun Wu, Maura O'Neill, Jinping Jia, Irene Collins, Mingfeng Zhang, Janelle V Thomas, Lauren M Rost, Sudipto Das, Hemang Parikh, Jefferson M Haake, Gail L Matters, Robert C Kurtz, William R Bamlet, Alison Klein, Rachael Stolzenberg-Solomon, Brian M Wolpin, Ronit Yarden, Zhaoming Wang, Jill Smith, Sara H Olson, Thorkell Andresson, Gloria M Petersen, Laufey T Amundadottir
Genome-wide association studies (GWAS) have identified multiple common susceptibility loci for pancreatic cancer. Here we report fine-mapping and functional analysis of one such locus residing in a 610 kb gene desert on chr13q22.1 (marked by rs9543325). The closest candidate genes, KLF5, KLF12, PIBF1, DIS3 and BORA, range in distance from 265-586 kb. Sequencing three sub-regions containing the top ranked SNPs by imputation P-value revealed a 30 bp insertion/deletion (indel) variant that was significantly associated with pancreatic cancer risk (rs386772267, P = 2...
August 30, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27546437/rna-decay-the-exosome-tramps-on-viral-rna
#20
Eytan Zlotorynski
No abstract text is available yet for this article.
August 22, 2016: Nature Reviews. Molecular Cell Biology
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