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Rna decay

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https://www.readbyqxmd.com/read/28742285/variable-expressivity-and-incomplete-penetrance-in-a-large-family-with-non-classical-diamond-blackfan-anemia-associated-with-ribosomal-protein-l11-splicing-variant
#1
Colleen M Carlston, Zeinab A Afify, Janice C Palumbos, Heidi Bagley, Carlos Barbagelata, Whitney L Wooderchak-Donahue, Rong Mao, John C Carey
Diamond-Blackfan anemia (DBA) is a group of clinically and genetically heterogeneous bone marrow failure disorders with or without congenital anomalies. Variable expressivity and incomplete penetrance have been observed within affected families. Diamond-Blackfan anemia-7 (DBA7), caused by heterozygous mutations in ribosomal protein L11 (RPL11), accounts for approximately 5% of DBA. DBA7 is usually characterized by early-onset bone marrow failure often accompanied by congenital malformations, especially thumb defects...
July 25, 2017: American Journal of Medical Genetics. Part A
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
#2
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/28740723/at-the-interface-of-three-nucleic-acids-the-role-of-rna-binding-proteins-and-poly-adp-ribose-in-dna-repair
#3
E E Alemasova, O I Lavrik
RNA-binding proteins (RBPs) regulate RNA metabolism, from synthesis to decay. When bound to RNA, RBPs act as guardians of the genome integrity at different levels, from DNA damage prevention to the post-transcriptional regulation of gene expression. Recently, RBPs have been shown to participate in DNA repair. This fact is of special interest as DNA repair pathways do not generally involve RNA. DNA damage in higher organisms triggers the formation of the RNA-like polymer - poly(ADP-ribose) (PAR). Nucleic acid-like properties allow PAR to recruit DNA- and RNA-binding proteins to the site of DNA damage...
April 2017: Acta Naturae
https://www.readbyqxmd.com/read/28710009/mrna-interactome-capture-in-mammalian-cells
#4
Nicolai Kastelic, Markus Landthaler
Throughout their entire life cycle, mRNAs are associated with RNA-binding proteins (RBPs), forming ribonucleoprotein (RNP) complexes with highly dynamic compositions. Their interplay is one key to control gene regulatory mechanisms from mRNA synthesis to decay. To assay the global scope of RNA-protein interactions, we and others have published a method combining crosslinking with highly stringent oligo(dT) affinity purification to enrich proteins associated with polyadenylated RNA (poly(A)+ RNA). Identification of the poly(A)+ RNA-bound proteome (also: mRNA interactome capture) has by now been applied to a diversity of cell lines and model organisms, uncovering comprehensive repertoires of RBPs and hundreds of novel RBP candidates...
July 11, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28709658/ngago-gdna-system-efficiently-suppresses-hepatitis-b-virus-replication-through-accelerating-decay-of-pregenomic-rna
#5
Zhuanchang Wu, Siyu Tan, Leiqi Xu, Lifen Gao, Haizhen Zhu, Chunhong Ma, Xiaohong Liang
Covalently closed circular DNA (cccDNA) in the hepatocytes nucleus is responsible for persistent infection of Hepatitis B virus (HBV). Current antiviral therapy drugs nucleos(t)ide analogs or interferon fail to eradicate HBV cccDNA. Genome editing technique provides an effective approach for HBV treatment through targeting viral cccDNA. Natronobacterium gregoryi Argonaute (NgAgo)-guide DNA (gDNA) system with powerful genome editing prompts us to explore its application in inhibiting HBV replication. Preliminary function verification indicated that NgAgo/EGFP-gDNA obviously inhibited EGFP expression...
July 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28708839/tumor-necrosis-factor-dynamically-regulates-the-mrna-stabilome-in-rheumatoid-arthritis-fibroblast-like-synoviocytes
#6
Konstantinos Loupasakis, David Kuo, Upneet K Sokhi, Christopher Sohn, Bethany Syracuse, Eugenia G Giannopoulou, Sung Ho Park, Hyelim Kang, Gunnar Rätsch, Lionel B Ivashkiv, George D Kalliolias
During rheumatoid arthritis (RA), Tumor Necrosis Factor (TNF) activates fibroblast-like synoviocytes (FLS) inducing in a temporal order a constellation of genes, which perpetuate synovial inflammation. Although the molecular mechanisms regulating TNF-induced transcription are well characterized, little is known about the impact of mRNA stability on gene expression and the impact of TNF on decay rates of mRNA transcripts in FLS. To address these issues we performed RNA sequencing and genome-wide analysis of the mRNA stabilome in RA FLS...
2017: PloS One
https://www.readbyqxmd.com/read/28706991/multiplexed-gene-control-reveals-rapid-mrna-turnover
#7
Antoine Baudrimont, Sylvia Voegeli, Eduardo Calero Viloria, Fabian Stritt, Marine Lenon, Takeo Wada, Vincent Jaquet, Attila Becskei
The rates of mRNA synthesis and decay determine the mRNA expression level. The two processes are under coordinated control, which makes the measurements of these rates challenging, as evidenced by the low correlation among the methods of measurement of RNA half-lives. We developed a minimally invasive method, multiplexed gene control, to shut off expression of genes with controllable synthetic promoters. The method was validated by measuring the ratios of the nascent to mature mRNA molecules and by measuring the half-life with endogenous promoters that can be controlled naturally or through inserting short sequences that impart repressibility...
July 2017: Science Advances
https://www.readbyqxmd.com/read/28705956/rapid-recovery-gene-downregulation-during-excess-light-stress-and-recovery-in-arabidopsis
#8
Peter Alexander Crisp, Diep Ganguly, Aaron B Smith, Kevin D Murray, Gonzalo M Estavillo, Iain R Searle, Ethan Ford, Ozren Bogdanović, Ryan Lister, Justin O Borevitz, Steven R Eichten, Barry J Pogson
Stress recovery may prove to be a promising approach to increase plant performance, and theoretically, mRNA instability may facilitate faster recovery. Transcriptome (RNA-seq, qPCR, sRNA-seq, PARE) and methylome profiling during repeated excess-light stress and recovery was performed at intervals as short as three minutes. We demonstrate that 87% of the stress-upregulated mRNAs analysed exhibit very rapid recovery. For instance, HSP101 abundance declined two-fold every 5.1 minutes. We term this phenomenon Rapid Recovery Gene Downregulation (RRGD), whereby mRNA abundance rapidly decreases promoting transcriptome resetting...
July 13, 2017: Plant Cell
https://www.readbyqxmd.com/read/28704426/rna-secondary-structure-and-nucleotide-composition-of-the-conserved-hallmark-sequence-of-leishmania-sider2-retroposons-are-essential-for-endonucleolytic-cleavage-and-mrna-degradation
#9
Hiva Azizi, Tatiany P Romão, Karen Santos Charret, Prasad K Padmanabhan, Osvaldo P de Melo Neto, Michaela Müller-McNicoll, Barbara Papadopoulou
We have reported previously that Short Interspersed Degenerate Retroposons of the SIDER2 subfamily, largely located within 3'UTRs of Leishmania transcripts, promote rapid turnover of mRNAs through endonucleolytic cleavage within the highly conserved second tandem 79-nt hallmark sequence (79-nt SII). Here, we used site-directed mutagenesis and in silico RNA structural studies to delineate the cis-acting requirements within 79-nt SII for cleavage and mRNA degradation. The putative cleavage site(s) and other nucleotides predicted to alter the RNA secondary structure of 79-nt SII were either deleted or mutated and their effect on mRNA turnover was monitored using a gene reporter system...
2017: PloS One
https://www.readbyqxmd.com/read/28686853/wdr26-haploinsufficiency-causes-a-recognizable-syndrome-of-intellectual-disability-seizures-abnormal-gait-and-distinctive-facial-features
#10
Cara M Skraban, Constance F Wells, Preetha Markose, Megan T Cho, Addie I Nesbitt, P Y Billie Au, Amber Begtrup, John A Bernat, Lynne M Bird, Kajia Cao, Arjan P M de Brouwer, Elizabeth H Denenberg, Ganka Douglas, Kristin M Gibson, Katheryn Grand, Alice Goldenberg, A Micheil Innes, Jane Juusola, Marlies Kempers, Esther Kinning, David M Markie, Martina M Owens, Katelyn Payne, Richard Person, Rolph Pfundt, Amber Stocco, Claire L S Turner, Nienke E Verbeek, Laurence E Walsh, Taylor C Warner, Patricia G Wheeler, Dagmar Wieczorek, Alisha B Wilkens, Evelien Zonneveld-Huijssoon, Tjitske Kleefstra, Stephen P Robertson, Avni Santani, Koen L I van Gassen, Matthew A Deardorff
We report 15 individuals with de novo pathogenic variants in WDR26. Eleven of the individuals carry loss-of-function mutations, and four harbor missense substitutions. These 15 individuals comprise ten females and five males, and all have intellectual disability with delayed speech, a history of febrile and/or non-febrile seizures, and a wide-based, spastic, and/or stiff-legged gait. These subjects share a set of common facial features that include a prominent maxilla and upper lip that readily reveal the upper gingiva, widely spaced teeth, and a broad nasal tip...
July 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28684539/ppr-polyadenylation-factor-defines-mitochondrial-mrna-identity-and-stability-in-trypanosomes
#11
Liye Zhang, Francois M Sement, Takuma Suematsu, Tian Yu, Stefano Monti, Lan Huang, Ruslan Aphasizhev, Inna Aphasizheva
In Trypanosoma brucei, most mitochondrial mRNAs undergo internal changes by RNA editing and 3' end modifications. The temporally separated and functionally distinct modifications are manifested by adenylation prior to editing, and by post-editing extension of a short A-tail into a long A/U-heteropolymer. The A-tail stabilizes partially and fully edited mRNAs, while the A/U-tail enables mRNA binding to the ribosome. Here, we identify an essential pentatricopeptide repeat-containing RNA binding protein, kinetoplast polyadenylation factor 3 (KPAF3), and demonstrate its role in protecting pre-mRNA against degradation by the processome...
July 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28684423/the-rna-binding-protein-hur-contributes-to-neuroinflammation-by-promoting-c-c-chemokine-receptor-6-ccr6-expression-on-th17-cells
#12
Jing Chen, Jennifer L Martindale, Carole Cramer, Myriam Gorospe, Ulus Atasoy, Paul D Drew, Shiguang Yu
In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). While many cytokines and their receptors are potently regulated via posttranscriptional mechanisms in response to various stimuli, how CCR6 expression is posttranscriptionally regulated in Th17 cells is unknown. Here, using RNA binding protein HuR conditional knockout (KO) and wild type (WT) mice, we present evidence that HuR posttranscriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28679534/hsp70-s-rna-binding-and-mrna-stabilizing-activities-are-independent-of-its-protein-chaperone-functions
#13
Aparna Kishor, Elizabeth J F White, Aerielle E Matsangos, Zisui Yan, Bishal Tandukar, Gerald M Wilson
Hsp70 is a protein chaperone that prevents protein aggregation and aids protein folding by binding to hydrophobic peptide domains through a reversible mechanism directed by an ATPase cycle. However, Hsp70 also binds U-rich RNA including some AU-rich elements (AREs) that regulate the decay kinetics of select mRNAs and has recently been shown to bind and stabilize some ARE-containing transcripts in cells. Previous studies indicated that both the ATP- and peptide-binding domains of Hsp70 contributed to the stability of Hsp70:RNA complexes and that ATP might inhibit RNA recruitment...
July 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28678879/treatment-with-integrase-inhibitor-suggests-a-new-interpretation-of-hiv-rna-decay-curves-that-reveals-a-subset-of-cells-with-slow-integration
#14
E Fabian Cardozo, Adriana Andrade, John W Mellors, Daniel R Kuritzkes, Alan S Perelson, Ruy M Ribeiro
The kinetics of HIV-1 decay under treatment depends on the class of antiretrovirals used. Mathematical models are useful to interpret the different profiles, providing quantitative information about the kinetics of virus replication and the cell populations contributing to viral decay. We modeled proviral integration in short- and long-lived infected cells to compare viral kinetics under treatment with and without the integrase inhibitor raltegravir (RAL). We fitted the model to data obtained from participants treated with RAL-containing regimes or with a four-drug regimen of protease and reverse transcriptase inhibitors...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28669802/the-rna-surveillance-factor-upf1-represses-myogenesis-via-its-e3%C3%A2-ubiquitin-ligase-activity
#15
Qing Feng, Sujatha Jagannathan, Robert K Bradley
UPF1 is an RNA helicase that orchestrates nonsense-mediated decay and other RNA surveillance pathways. While UPF1 is best known for its basal cytoprotective role in degrading aberrant RNAs, UPF1 also degrades specific, normally occurring mRNAs to regulate diverse cellular processes. Here we describe a role for UPF1 in regulated protein decay, wherein UPF1 acts as an E3 ubiquitin ligase to repress human skeletal muscle differentiation. Suppressing UPF1 accelerates myogenesis, while ectopically increasing UPF1 levels slows myogenesis...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28663146/human-nonsense-mediated-rna-decay-regulates-emt-by-targeting-the-tgf-%C3%A3-signaling-pathway-in-lung-adenocarcinoma
#16
Lu Cao, Lisha Qi, Lin Zhang, Wangzhao Song, Yue Yu, Cong Xu, Lingmei Li, Yuhong Guo, Lingyi Yang, Changxu Liu, Qiujuan Huang, Yalei Wang, Baocun Sun, Bin Meng, Bin Zhang, Wenfeng Cao
Nonsense-mediated mRNA decay (NMD) is a highly conserved pathway that selectively degrades aberrant RNA transcripts. In this study, we proved that NMD regulates the epithelial-mesenchymal transition (EMT) of lung adenocarcinoma (ADC). Moreover, we found that NMD core factor UP-frameshift 1 tends to be expressed at lower levels in human ADC tissues than in normal lung tissues, thereby raising the possibility that NMD may be downregulated to permit ADC oncogenesis. Our experiments in human ADC cell lines showed that downregulating NMD can promote EMT...
June 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28663102/rnase-h1-dependent-antisense-oligonucleotides-are-robustly-active-in-directing-rna-cleavage-in-both-the-cytoplasm-and-the-nucleus
#17
Xue-Hai Liang, Hong Sun, Joshua G Nichols, Stanley T Crooke
RNase H1-dependent antisense oligonucleotides (ASOs) are active in reducing levels of both cytoplasmic mRNAs and nuclear retained RNAs. Although ASO activity in the nucleus has been well demonstrated, the cytoplasmic activity of ASOs is less clear. Using kinetic and subcellular fractionation studies, we evaluated ASO activity in the cytoplasm. Upon transfection, ASOs targeting exonic regions rapidly reduced cytoplasmically enriched mRNAs, whereas an intron-targeting ASO that only degrades the nuclear pre-mRNA reduced mRNA levels at a slower rate, similar to normal mRNA decay...
June 26, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28663100/a-new-aav10-u7-mediated-gene-therapy-prolongs-survival-and-restores-function-in-an-als-mouse-model
#18
Maria Grazia Biferi, Mathilde Cohen-Tannoudji, Ambra Cappelletto, Benoit Giroux, Marianne Roda, Stéphanie Astord, Thibaut Marais, Corinne Bos, Thomas Voit, Arnaud Ferry, Martine Barkats
One of the most promising therapeutic approaches for familial amyotrophic lateral sclerosis linked to superoxide dismutase 1 (SOD1) is the suppression of toxic mutant SOD1 in the affected tissues. Here, we report an innovative molecular strategy for inducing substantial, widespread, and sustained reduction of mutant human SOD1 (hSOD1) levels throughout the body of SOD1(G93A) mice, leading to therapeutic effects in animals. Adeno-associated virus serotype rh10 vectors (AAV10) were used to mediate exon skipping of the hSOD1 pre-mRNA by expression of exon-2-targeted antisense sequences embedded in a modified U7 small-nuclear RNA (AAV10-U7-hSOD)...
June 26, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28655137/alzheimer-s-disease-genetics-and-abca7-splicing
#19
Jared B Vasquez, James F Simpson, Ryan Harpole, Steven Estus
Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer's disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro...
June 22, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28654916/inhibition-of-cox2-enhances-the-chemosensitivity-of-dichloroacetate-in-cervical-cancer-cells
#20
Bo Li, Xinzhe Li, Haojun Xiong, Peng Zhou, Zhenhong Ni, Teng Yang, Yan Zhang, Yijun Zeng, Jintao He, Fan Yang, Nan Zhang, Yuting Wang, Yingru Zheng, Fengtian He
Dichloroacetate (DCA), a traditional mitochondria-targeting agent, has shown promising prospect as a sensitizer in fighting against malignancies including cervical cancer. But it is unclear about the effect of DCA alone on cervical tumor. Moreover, previous reports have demonstrated that the increased cyclooxygenase-2 (COX2) expression is associated with chemoresistance and poor prognosis of cervical cancer. However, it is still unknown whether COX2 can affect the sensitivity of DCA in cervical cancer cells...
June 16, 2017: Oncotarget
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