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Rna decay

Katarzyna Bartkowska, Beata Tepper, Kris Turlejski, Ruzanna L Djavadian
The exon junction complex (EJC) consists of four core proteins: Magoh, RNA-binding motif 8A (Rbm8a, also known as Y14), eukaryotic initiation factor 4A3 (eIF4A3, also known as DDX48), and metastatic lymph node 51 (MLN51, also known as Casc3 or Barentsz), which are involved in the regulation of many processes occurring between gene transcription and protein translation. Its main role is to assemble into spliceosomes at the exon-exon junction of mRNA during splicing. It is, therefore, a range of functions concerning post-splicing events such as mRNA translocation, translation, and nonsense-mediated mRNA decay (NMD)...
May 23, 2018: Reviews in the Neurosciences
Wanyan Tan, Wei Wang, Qingfeng Ma
Serine/arginine-rich splicing factors (SRSFs) have one or two RNA recognition motifs in the N terminal and a serine/arginine-enriched domain in the C terminal. SRSFs are essential components of spliceosomes and are involved in alternative splicing, spliceosome assembly, mRNA export, and nonsense-mediated mRNA decay. The maintenance of cellular and tissue homeostasis relies on accurate alternative splicing, and various patterns of abnormal alternative splicing can cause different diseases. SRSF4 is associated with many physiological and pathological processes and has applications in the diagnosis and prognosis of specific diseases...
2018: BioMed Research International
Xing Liu, Rui Fu, Youdong Pan, Karla F Meza-Sosa, Zhibin Zhang, Judy Lieberman
Widespread mRNA decay, an unappreciated feature of apoptosis, enhances cell death and depends on mitochondrial outer membrane permeabilization (MOMP), TUTases, and DIS3L2. Which RNAs are decayed and the decay-initiating event are unknown. Here, we show extensive decay of mRNAs and poly(A) noncoding (nc)RNAs at the 3' end, triggered by the mitochondrial intermembrane space 3'-to-5' exoribonuclease PNPT1, released during MOMP. PNPT1 knockdown inhibits apoptotic RNA decay and reduces apoptosis, while ectopic expression of PNPT1, but not an RNase-deficient mutant, increases RNA decay and cell death...
May 10, 2018: Cell
Vanessa L Lattimore, John F Pearson, Margaret J Currie, Amanda B Spurdle, Bridget A Robinson, Logan C Walker
PCR-based RNA splicing assays are commonly used in diagnostic and research settings to assess the potential effects of variants of uncertain clinical significance in BRCA1 and BRCA2 . The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium completed a multicentre investigation to evaluate differences in assay design and the integrity of published data, raising a number of methodological questions associated with cell culture conditions and PCR-based protocols. We utilized targeted RNA-seq to re-assess BRCA1 and BRCA2 mRNA isoform expression patterns in lymphoblastoid cell lines (LCLs) previously used in the multicentre ENIGMA study...
2018: Frontiers in Oncology
Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A Crandall, Nathan Edwards, Anelia Horvath
Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Scientific Reports
Jan Marchant, Ad Bax, Michael F Summers
NMR approaches using nucleotide-specific deuterium labeling schemes have enabled structural studies of biologically relevant RNAs of increasing size and complexity. Although local structure is well-determined using these methods, definition of global structural features, including relative orientations of independent helices, remains a challenge. Residual dipolar couplings, a potential source of orientation information, have not been obtainable for large RNAs due to poor sensitivity resulting from rapid heteronuclear signal decay...
May 14, 2018: Journal of the American Chemical Society
Liang Guo, Irina Vlasova-St Louis, Paul R Bohjanen
Viruses alter host-cell gene expression at many biochemical levels, such as transcription, translation, mRNA splicing and mRNA decay in order to create a cellular environment suitable for viral replication. In this review, we discuss mechanisms by which viruses manipulate host-gene expression at the level of mRNA decay in order to enable the virus to evade host antiviral responses to allow viral survival and replication. We discuss different cellular RNA decay pathways, including the deadenylation-dependent mRNA decay pathway, and various strategies that viruses exploit to manipulate these pathways in order to create a virus-friendly cellular environment...
March 2018: Future Virology
Manfred Schmid, Torben Heick Jensen
RNA turnover is an integral part of cellular RNA homeostasis and gene expression regulation. Whereas the cytoplasmic control of protein-coding mRNA is often the focus of study, we discuss here the less appreciated role of nuclear RNA decay systems in controlling RNA polymerase II (RNAPII)-derived transcripts. Historically, nuclear RNA degradation was found to be essential for the functionalization of transcripts through their proper maturation. Later, it was discovered to also be an important caretaker of nuclear hygiene by removing aberrant and unwanted transcripts...
May 10, 2018: Nature Reviews. Genetics
Ang Gao, Nikita Vasilyev, Daniel J Luciano, Rose Levenson-Palmer, Jamie Richards, William M Marsiglia, Nathaniel J Traaseth, Joel G Belasco, Alexander Serganov
Vitally important for controlling gene expression in eukaryotes and prokaryotes, the deprotection of mRNA 5' termini is governed by enzymes whose activity is modulated by interactions with ancillary factors. In Escherichia coli, 5'-end-dependent mRNA degradation begins with the generation of monophosphorylated 5' termini by the RNA pyrophosphohydrolase RppH, which can be stimulated by DapF, a diaminopimelate epimerase involved in amino acid and cell wall biosynthesis. We have determined crystal structures of RppH-DapF complexes and measured rates of RNA deprotection...
May 4, 2018: Nucleic Acids Research
Weijun Chen, Jill Moore, Hakan Ozadam, Hennady P Shulha, Nicholas Rhind, Zhiping Weng, Melissa J Moore
Full understanding of eukaryotic transcriptomes and how they respond to different conditions requires deep knowledge of all sites of intron excision. Although RNA sequencing (RNA-seq) provides much of this information, the low abundance of many spliced transcripts (often due to their rapid cytoplasmic decay) limits the ability of RNA-seq alone to reveal the full repertoire of spliced species. Here, we present "spliceosome profiling," a strategy based on deep sequencing of RNAs co-purifying with late-stage spliceosomes...
May 3, 2018: Cell
Eric J Montemayor, Allison L Didychuk, Allyson D Yake, Gurnimrat K Sidhu, David A Brow, Samuel E Butcher
The spliceosome removes introns from precursor messenger RNA (pre-mRNA) to produce mature mRNA. Prior to catalysis, spliceosomes are assembled de novo onto pre-mRNA substrates. During this assembly process, U6 small nuclear RNA (snRNA) undergoes extensive structural remodeling. The early stages of this remodeling process are chaperoned by U6 snRNP proteins Prp24 and the Lsm2-8 heteroheptameric ring. We now report a structure of the U6 snRNP from Saccharomyces cerevisiae. The structure reveals protein-protein contacts that position Lsm2-8 in close proximity to the chaperone "active site" of Prp24...
May 1, 2018: Nature Communications
David Polo, Julien Schaeffer, Peter Teunis, Vincent Buchet, Françoise S Le Guyader
Oysters, being filter feeders, can accumulate some human pathogens such as norovirus, a highly infectious calicivirus, most common cause of acute gastroenteritis worldwide. Accumulated virus decays over a period of days to weeks, possibly rendering contaminated oysters safe again. Sensitive molecular methods have been set up for shellfish analysis but without answering the question of infectious virus detection. Using the Tulane virus (TV), a norovirus surrogate that recognizes the same ligand as human norovirus in oyster tissues, the genome and infectious virus decay rates were estimated using inverse linear regression in a Bayesian framework for genome copies...
2018: Frontiers in Microbiology
Alexandre Le Scornet, Peter Redder
Opportunistic pathogens have to be ready to change life-style whenever the occasion arises, and therefore need to keep tight control over the expression of their virulence factors. Doubly so for commensal bacteria, such as Staphylococcus aureus, which should avoid harming their hosts when they are in a state of peaceful co-existence. S. aureus carries very few sigma factors to help define the transcriptional programs, but instead uses a plethora of small RNA molecules and RNA-RNA interactions to regulate gene expression post-transcriptionally...
April 26, 2018: Biochimica et Biophysica Acta
Arlo Radtke, Finja Hennig, Raphael Ikogho, Johannes Hammel, Petra Anheuser, Christian Wülfing, Gazanfer Belge, Klaus-Peter Dieckmann
BACKGROUND: Accumulating evidence suggests serum levels of microRNA (miR)-371a-3p to be a novel tumour marker of testicular germ cell tumours (GCTs). Presently, there is only limited information regarding the velocity of decline of serum levels in response to treatment. PATIENTS AND METHODS: Twenty-four patients with testicular GCT (20 seminoma, 4 nonseminoma, median age 40 years) with clinical stage 1 had measurements of serum levels of miR-371a-3p preoperatively and repeatedly on the following 3 days...
April 26, 2018: Urologia Internationalis
Jaewoo Choi, Kyutae Lee, Kristin Ingvarsdottir, Roberto Bonasio, Anita Saraf, Laurence Florens, Michael P Washburn, Saber Tadros, Michael R Green, Luca Busino
Kelch-like protein 6 (KLHL6) is an uncharacterized gene mutated in diffuse large B-cell lymphoma (DLBCL). Here we report that KLHL6 assembles with cullin3 to form a functional cullin-RING ubiquitin ligase. Mutations in KLHL6 inhibit its ligase activity by disrupting the interaction with cullin3. Loss of KLHL6 favours DLBCL growth and survival both in vitro and in xenograft models. We further established that the mRNA decay factor roquin2 is a substrate of KLHL6. Degradation of roquin2 is dependent on B-cell receptor activation, and requires the integrity of the Tyr691 residue in roquin2 that is essential for its interaction with KLHL6...
May 2018: Nature Cell Biology
Ute Scheller, Kathrin Pfisterer, Steffen Uebe, Arif B Ekici, André Reis, Rami Jamra, Fulvia Ferrazzi
BACKGROUND: Decapping of mRNA is an important step in the regulation of mRNA turnover and therefore of gene expression, which is a key process controlling development and homeostasis of all organisms. It has been shown that EDC3 plays a role in mRNA decapping, however its function is not well understood. Previously, we have associated a homozygous variant in EDC3 with autosomal recessive intellectual disability. Here, we investigate the functional role of EDC3. METHODS: We performed transcriptome analyses in patients' samples...
April 23, 2018: BMC Medical Genomics
Ana Rachel Leda, James Hunter, Ursula Castro Oliveira, Inacio Junqueira Azevedo, Maria Cecilia Araripe Sucupira, Ricardo Sobhie Diaz
Objectives: The presence of minority transmitted drug resistance mutations was assessed using ultra-deep sequencing and correlated with disease progression among recently HIV-1-infected individuals from Brazil. Methods: Samples at baseline during recent infection and 1 year after the establishment of the infection were analysed. Viral RNA and proviral DNA from 25 individuals were subjected to ultra-deep sequencing of the reverse transcriptase and protease regions of HIV-1...
April 19, 2018: Journal of Antimicrobial Chemotherapy
Huajun Zhang, Xiaolin Huang, Lei Huang, Fangjian Bao, Shangling Xiong, Kai Wang, Demin Zhang
The determinants of microeukaryotic biogeography in coastal waters at a regional scale remain largely unclear. The coastal northern Zhejiang (in the East China Sea) is a typical subtropical marine ecosystem with multiple environmental gradients that has been extensively perturbed by anthropogenic activities. Thus, it is a valuable region to investigate the key drivers that shape microbial biogeography. We investigated microeukaryotic communities in surface waters from 115 stations in this region using 18S ribosomal RNA gene amplicon sequencing...
April 18, 2018: Science of the Total Environment
Bijoy K Mohanty, Sidney R Kushner
Gene expression in Gram-negative bacteria is regulated at many levels, including transcription initiation, RNA processing, RNA/RNA interactions, mRNA decay, and translational controls involving enzymes that alter translational efficiency. In this review, we discuss the various enzymes that control transcription, translation, and RNA stability through RNA processing and degradation. RNA processing is essential to generate functional RNAs, while degradation helps control the steady-state level of each individual transcript...
April 2018: Microbiology Spectrum
István Szádeczky-Kardoss, Tibor Csorba, Andor Auber, Anita Schamberger, Tünde Nyikó, János Taller, Tamás I Orbán, József Burgyán, Dániel Silhavy
Translation-dependent mRNA quality control systems protect the protein homeostasis of eukaryotic cells by eliminating aberrant transcripts and stimulating the decay of their protein products. Although these systems are intensively studied in animals, little is known about the translation-dependent quality control systems in plants. Here, we characterize the mechanism of nonstop decay (NSD) system in Nicotiana benthamiana model plant. We show that plant NSD efficiently degrades nonstop mRNAs, which can be generated by premature polyadenylation, and stop codon-less transcripts, which are produced by endonucleolytic cleavage...
April 17, 2018: Nucleic Acids Research
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