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mRNA decay

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https://www.readbyqxmd.com/read/28231257/targeted-sequencing-identifies-a-novel-sh2d1a-pathogenic-variant-in-a-chinese-family-carrier-screening-and-prenatal-genetic-testing
#1
Jun-Yu Zhang, Song-Chang Chen, Yi-Yao Chen, Shu-Yuan Li, Lan-Lan Zhang, Ying-Hua Shen, Chun-Xin Chang, Yu-Qian Xiang, He-Feng Huang, Chen-Ming Xu
X-linked lymphoproliferative disease type 1 (XLP1) is a rare primary immunodeficiency characterized by a clinical triad consisting of severe EBV-induced hemophagocytic lymphohistiocytosis, B-cell lymphoma, and dysgammaglobulinemia. Mutations in SH2D1A gene have been revealed as the cause of XLP1. In this study, a pregnant woman with recurrence history of birthing immunodeficiency was screened for pathogenic variant because the proband sample was unavailable. We aimed to clarify the genetic diagnosis and provide prenatal testing for the family...
2017: PloS One
https://www.readbyqxmd.com/read/28224650/androgen-receptor-splice-variants-are-not-substrates-of-nonsense-mediated-decay
#2
Atinuke S Ajiboye, David Esopi, Srinivasan Yegnasubramanian, Samuel R Denmeade
BACKGROUND: Androgen receptor (AR) splice variants have been clinically associated with progressive cancer, castration-resistance, and resistance to AR antagonists and androgen synthesis inhibitors. AR variants can be generated by genomic alterations and alternative splicing, and their expression is androgen-regulated. There has been a suggestion that AR variants bearing premature termination codons and coding for truncated proteins should be regulated by the nonsense-mediated decay (NMD) mRNA surveillance pathway, suggesting that either the NMD pathway is dysfunctional in variant-expressing cell lines or that variants are somehow able to evade degradation by NMD...
February 22, 2017: Prostate
https://www.readbyqxmd.com/read/28219744/metabolic-labeling-and-recovery-of-nascent-rna-to-accurately-quantify-mrna-stability
#3
Joseph Russo, Adam M Heck, Jeffrey Wilusz, Carol J Wilusz
Changes in the rate of mRNA decay are closely coordinated with transcriptional changes and together these events have profound effects on gene expression during development and disease. Traditional approaches to assess mRNA decay have relied on inhibition of transcription, which can alter mRNA decay rates and confound interpretation. More recently, metabolic labeling combined with chemical modification and fractionation of labeled RNAs has allowed the isolation of nascent transcripts and the subsequent calculation of mRNA decay rates...
February 17, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28219207/-mutations-of-vitamin-d-receptor-gene-found-in-patients-with-multiple-myeloma
#4
Y Liu, H B Rui
Objective: To explore the mutations of vitamin D receptor (VDR) gene in patients with multiple myeloma (MM). Methods: Polymerase chain reaction (PCR) and direct DNA sequencing were used to detect the mutations of VDR gene(loci Fok Ⅰ, Bsm Ⅰ, Apa Ⅰ, Taq Ⅰ) in forty MM cases and 84 healthy control subjects. Results: A synonymous mutation (ATC→ATA , both encode isoleucine) at cDNA codon1421 of VDR gene was found in one MM patients, which correlated to a better therapeutic response. Rare Bsm Ⅰ AA genotype and Taq Ⅰ CC genotype were detected in a MM patient, which might be related to the relapsing and refracfory disease...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28213379/slowed-decay-of-mrnas-enhances-platelet-specific-translation
#5
Eric W Mills, Rachel Green, Nicholas T Ingolia
Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of mRNAs, ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the full scope of platelet translation have remained elusive. Using RNA-Seq and ribosome profiling of primary human platelets, we show the platelet transcriptome encompasses a subset of transcripts detected by RNA-Seq analysis of in vitro derived MK cells and these platelet-enriched transcripts are broadly occupied by ribosomes...
February 17, 2017: Blood
https://www.readbyqxmd.com/read/28209632/high-resolution-profiling-of-nmd-targets-in-yeast-reveals-translational-fidelity-as-a-basis-for-substrate-selection
#6
Alper Celik, Richard Baker, Feng He, Allan Jacobson
Nonsense-mediated mRNA decay (NMD) plays an important role in eukaryotic gene expression yet the scope and the defining features of NMD-targeted transcripts remain elusive. To address these issues, we re-evaluated the genome-wide expression of annotated transcripts in yeast cells harboring deletions of the UPF1, UPF2, or UPF3 genes. Our new RNA-Seq analyses confirm previous results of microarray studies, but also uncover hundreds of new NMD-regulated transcripts that had escaped previous detection, including many intron-containing pre-mRNAs and several non-coding RNAs...
February 16, 2017: RNA
https://www.readbyqxmd.com/read/28194024/regnase-1-a-rapid-response-ribonuclease-regulating-inflammation-and-stress-responses
#7
REVIEW
Renfang Mao, Riyun Yang, Xia Chen, Edward W Harhaj, Xiaoying Wang, Yihui Fan
RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28193672/translation-of-poly-a-tails-leads-to-precise-mrna-cleavage
#8
Nicholas R Guydosh, Rachel Green
Translation of poly(A) tails leads to mRNA cleavage but the mechanism and global pervasiveness of this "nonstop/no-go" decay process is not understood. Here we performed ribosome profiling (in a yeast strain lacking exosome function) of short 15-18 nt mRNA footprints to identify ribosomes stalled at 3' ends of mRNA decay intermediates. In this background, we found mRNA cleavage extending hundreds of nucleotides upstream of ribosome stalling in poly(A) and predominantly in one reading frame. These observations suggest that decay-triggering endonucleolytic cleavage is closely associated with the ribosome...
February 13, 2017: RNA
https://www.readbyqxmd.com/read/28192787/m-6-a-dependent-maternal-mrna-clearance-facilitates-zebrafish-maternal-to-zygotic-transition
#9
Boxuan Simen Zhao, Xiao Wang, Alana V Beadell, Zhike Lu, Hailing Shi, Adam Kuuspalu, Robert K Ho, Chuan He
The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N(6)-methyladenosine (m(6)A) modified, and the clearance of these maternal mRNAs is facilitated by an m(6)A-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of m(6)A-modified maternal mRNAs and impedes zygotic genome activation...
February 23, 2017: Nature
https://www.readbyqxmd.com/read/28191469/rna-binding-protein-dnd1-promotes-breast-cancer-apoptosis-by-stabilizing-the-bim-mrna-in-a-mir-221-binding-site
#10
Feng Cheng, Ying Pan, Yi-Min Lu, Lei Zhu, Shuzheng Chen
RNA-binding proteins (RBPs) and miRNAs are capable of controlling processes in normal development and cancer. Both of them could determine RNA transcripts fate from synthesis to decay. One such RBP, Dead end (Dnd1), is essential for regulating germ-cell viability and suppresses the germ-cell tumors development, yet how it exerts its functions in breast cancer has remained unresolved. The level of Dnd1 was detected in 21 cancerous tissues paired with neighboring normal tissues by qRT-PCR. We further annotated TCGA (The Cancer Genome Atlas) mRNA expression profiles and found that the expression of Dnd1 and Bim is positively correlated (p = 0...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28190770/nuclear-rna-decay-pathways-aid-rapid-remodeling-of-gene-expression-in-yeast
#11
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...
January 27, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28188930/microrna-135a-regulates-sodium-calcium-exchanger-gene-expression-and-cardiac-electrical-activity
#12
Eric Duong, Jiening Xiao, Xiao Yan Qi, Stanley Nattel
BACKGROUND: Complete atrioventricular block (CAVB) causes arrhythmogenic remodeling and increases the risk of Torsades de Pointes (TdP) arrhythmias. MicroRNAs (miRNAs) are key regulators of gene-expression that contribute to cardiac remodeling. OBJECTIVE: To assess miRNA changes after complete atrioventricular block (CAVB) and identify novel candidates potentially involved in arrhythmogenic cardiac remodeling. METHODS: CAVB was induced in mice via His bundle ablation...
February 7, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28188297/alternative-splicing-in-the-cytochrome-p450-superfamily-expands-protein-diversity-to-augment-gene-function-and-redirect-human-drug-metabolism
#13
Andrew J Annalora, Craig B Marcus, Patrick L Iversen
The human genome encodes 57 cytochrome P450 (CYP) genes whose enzyme products metabolize hundreds of drugs, thousands of xenobiotics and unknown numbers of endogenous compounds including steroids, retinoids and icosinoids. Indeed, CYP genes are the first line of defense against daily environmental chemical challenges in a manner that parallels the immune system. Several databases, including PubMed, AceView, and Ensembl, were queried to establish a comprehensive analysis of the full human CYP transcriptome. This review describes a remarkable diversification of the 57 human CYP genes, which may be alternatively processed into nearly 1000 distinct mRNA transcripts to shape an individual's CYP proteome...
February 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28183797/ca-2-binding-protein-2-inhibits-ca-2-channel-inactivation-in-mouse-inner-hair-cells
#14
Maria Magdalena Picher, Anna Gehrt, Sandra Meese, Aleksandra Ivanovic, Friederike Predoehl, SangYong Jung, Isabelle Schrauwen, Alberto Giulio Dragonetti, Roberto Colombo, Guy Van Camp, Nicola Strenzke, Tobias Moser
Ca(2+)-binding protein 2 (CaBP2) inhibits the inactivation of heterologously expressed voltage-gated Ca(2+) channels of type 1.3 (CaV1.3) and is defective in human autosomal-recessive deafness 93 (DFNB93). Here, we report a newly identified mutation in CABP2 that causes a moderate hearing impairment likely via nonsense-mediated decay of CABP2-mRNA. To study the mechanism of hearing impairment resulting from CABP2 loss of function, we disrupted Cabp2 in mice (Cabp2(LacZ/LacZ) ). CaBP2 was expressed by cochlear hair cells, preferentially in inner hair cells (IHCs), and was lacking from the postsynaptic spiral ganglion neurons (SGNs)...
February 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28163695/acth-action-on-messenger-rna-stability-mechanisms
#15
Agnès Desroches-Castan, Jean-Jacques Feige, Nadia Cherradi
The regulation of mRNA stability has emerged as a critical control step in dynamic gene expression. This process occurs in response to modifications of the cellular environment, including hormonal variations, and regulates the expression of subsets of proteins whose levels need to be rapidly adjusted. Modulation of messenger RNA stability is usually mediated by stabilizing or destabilizing RNA-binding proteins (RNA-BP) that bind to the 3'-untranslated region regulatory motifs, such as AU-rich elements (AREs)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28157501/when-lin41-comes-to-a-fork-in-the-road-it-takes-both-paths-translational-repression-or-mrna-decay-depending-on-the-target-site-position
#16
Jacqelyn M Hand, Ariel A Bazzini
In this issue, Aeschimann et al. (2017) demonstrate that, depending on the target location site (5'UTR or 3'UTR), LIN41 triggers repression of translation or mRNA decay, suggesting that one factor may use two independent pathways of post-transcriptional gene regulation.
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28157223/novel-variants-in-pax6-gene-caused-congenital-aniridia-in-two-chinese-families
#17
R Zhang, S Linpeng, X Wei, H Li, Y Huang, J Guo, Q Wu, D Liang, L Wu
PurposeTo reveal the underlying genetic defect in two four-generation Chinese families with aniridia and explore the pathologic mechanism.MethodsFull ophthalmic examinations were performed in two families with aniridia. The PAX6 gene was directly sequenced in patients of two families, and the detected variants were screened in unaffected family members and two hundred unrelated healthy controls. Real-time quantitative PCR was used to explore pathologic mechanisms of the two variants.ResultsAniridia, cataract, and oscillatory nystagmus were observed in patients of the two families...
February 3, 2017: Eye
https://www.readbyqxmd.com/read/28145797/characterisation-of-new-generation-aminoglycoside-promoting-premature-termination-codon-readthrough-in-cancer-cells
#18
Laure Bidou, Olivier Bugaud, Valery Belakhov, Timor Baasov, Olivier Namy
Nonsense mutations, generating premature termination codons (PTCs), account for 10% to 30% of the mutations in tumour suppressor genes. Nonsense translational suppression, induced by small molecules including gentamicin and G418, has been suggested as a potential therapy to counteract the deleterious effects of nonsense mutations in several genetic diseases and cancers. We describe here that NB124, a synthetic aminoglycoside derivative recently developed especially for PTC suppression, strongly induces apoptosis in human tumour cells by promoting high level of PTC readthrough...
February 1, 2017: RNA Biology
https://www.readbyqxmd.com/read/28144752/novel-fam134b-mutations-and-their-clinicopathological-significance-in-colorectal-cancer
#19
Farhadul Islam, Vinod Gopalan, Riajul Wahab, Katherine Ting-Wei Lee, Md Hakimul Haque, Afraa Mamoori, Cu-Tai Lu, Robert A Smith, Alfred K-Y Lam
FAM134B is a putative tumour suppressor gene and no mutations in FAM134B have been reported in colorectal cancer (CRC) to date. This study aims to identify FAM134B mutation sites and the clinicopathological significance of the gene in patients with CRC. Eighty-eight colorectal cancers were studied for FAM134B mutations by Sanger sequencing. The mutations in these cancers were then tested for correlations with the clinical and pathological parameters of the studied cancers. In addition, mRNA and protein expression of FAM134B in colorectal cancers was examined by polymerase chain reaction, Western blots, and immunofluorescence analysis...
January 31, 2017: Human Genetics
https://www.readbyqxmd.com/read/28143407/widespread-changes-in-mrna-stability-contribute-to-quiescence-specific-gene-expression-patterns-in-a-fibroblast-model-of-quiescence
#20
Elizabeth L Johnson, David G Robinson, Hilary A Coller
BACKGROUND: Quiescence, reversible exit from the cell division cycle, is characterized by large-scale changes in steady-state gene expression, yet mechanisms controlling these changes are in need of further elucidation. In order to characterize the effects of post-transcriptional control on the quiescent transcriptome in human fibroblasts, we determined mRNA decay rates for over 10,000 genes using a transcription shut-off time-course. RESULTS: We found that ~500 of the genes monitored exhibited significant changes in decay rate upon quiescence induction...
February 1, 2017: BMC Genomics
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