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https://www.readbyqxmd.com/read/27932504/expression-of-cav1-3-calcium-channel-in-the-human-and-mouse-colon-post-transcriptional-inhibition-by-ifn%C3%AE
#1
Vijayababu M Radhakrishnan, Maryam M Gilpatrick, Nouralhoda Dehdashti, Pawel R Kiela, Fayez K Ghishan
It has been hypothesized that apically expressed L-type Ca(2+) channel Cav1.3 (encoded by CACNA1D gene) contributes towards an alternative TRPV6-independent route of intestinal epithelial Ca(2+) absorption, especially during digestion when high luminal concentration of Ca(2+) and other nutrients limit TRPV6 contribution. We and others have implicated altered expression and activity of key mediators of intestinal and renal Ca(2+) (re)absorption as contributors to negative systemic Ca2+ balance and bone loss in intestinal inflammation...
December 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27927164/the-role-of-nucleotide-composition-in-premature-termination-codon-recognition
#2
Fouad Zahdeh, Liran Carmel
BACKGROUND: It is not fully understood how a termination codon is recognized as premature (PTC) by the nonsense-mediated decay (NMD) machinery. This is particularly true for transcripts lacking an exon junction complex (EJC) along their 3' untranslated region (3'UTR), and thus degrade through the EJC-independent NMD pathway. RESULTS: Here, we analyzed data of transcript stability change following NMD repression and identified over 200 EJC-independent NMD-targets...
December 7, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27918561/a-human-microprotein-that-interacts-with-the-mrna-decapping-complex
#3
Nadia G D'Lima, Jiao Ma, Lauren Winkler, Qian Chu, Ken H Loh, Elizabeth O Corpuz, Bogdan A Budnik, Jens Lykke-Andersen, Alan Saghatelian, Sarah A Slavoff
Proteomic detection of non-annotated microproteins indicates the translation of hundreds of small open reading frames (smORFs) in human cells, but whether these microproteins are functional or not is unknown. Here, we report the discovery and characterization of a 7-kDa human microprotein we named non-annotated P-body dissociating polypeptide (NoBody). NoBody interacts with mRNA decapping proteins, which remove the 5' cap from mRNAs to promote 5'-to-3' decay. Decapping proteins participate in mRNA turnover and nonsense-mediated decay (NMD)...
December 5, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27917860/interrogating-the-degradation-pathways-of-unstable-mrnas-with-xrn1-resistant-sequences
#4
Volker Boehm, Jennifer V Gerbracht, Marie-Charlotte Marx, Niels H Gehring
The turnover of messenger RNAs (mRNAs) is a key regulatory step of gene expression in eukaryotic cells. Due to the complexity of the mammalian degradation machinery, the contribution of decay factors to the directionality of mRNA decay is poorly understood. Here we characterize a molecular tool to interrogate mRNA turnover via the detection of XRN1-resistant decay fragments (xrFrag). Using nonsense-mediated mRNA decay (NMD) as a model pathway, we establish xrFrag analysis as a robust indicator of accelerated 5'-3' mRNA decay...
December 5, 2016: Nature Communications
https://www.readbyqxmd.com/read/27911957/tristetraprolin-down-regulation-contributes-to-persistent-tnf-alpha-expression-induced-by-cigarette-smoke-extract-through-a-post-transcriptional-mechanism
#5
Xue-Ke Zhao, Pulin Che, Ming-Liang Cheng, Quan Zhang, Mao Mu, Hong Li, Yuan Luo, Yue-Dong Liang, Xin-Hua Luo, Chang-Qing Gao, Patricia L Jackson, J Michael Wells, Yong Zhou, Meng Hu, Guoqiang Cai, Victor J Thannickal, Chad Steele, J Edwin Blalock, Xiaosi Han, Ching-Yi Chen, Qiang Ding
RATIONALE: Tumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory mediator and its expression is up-regulated in chronic obstructive pulmonary disease (COPD). Tristetraprolin (TTP) is implicated in regulation of TNF-α expression; however, whether TTP is involved in cigarette smoke-induced TNF-α expression has not been determined. METHODS: TTP expression was examined by western blot analysis in murine alveolar macrophages and alveolar epithelial cells challenged without or with cigarette smoke extract (CSE)...
2016: PloS One
https://www.readbyqxmd.com/read/27905550/deep-sequencing-of-transcriptome-profiling-of-gstm2-knock-down-in-swine-testis-cells
#6
Yuqi Lv, Yi Jin, Yongqiang Zhou, Jianjun Jin, Zhenfa Ma, Zhuqing Ren
Glutathione-S-transferases mu 2 (GSTM2), a kind of important Phase II antioxidant enzyme of eukaryotes, is degraded by nonsense mediated mRNA decay due to a C27T substitution in the fifth exon of pigs. As a reproductive performance-related gene, GSTM2 is involved in embryo implantation, whereas, functional deficiency of GSTM2 induces pre- or post-natal death in piglets potentially. To have some insight into the role of GSTM2 in embryo development, high throughput RNA sequencing is performed using the swine testis cells (ST) with the deletion of GSTM2...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905021/netherton-syndrome-a-genotype-phenotype-review
#7
REVIEW
Constantina A Sarri, Angeliki Roussaki-Schulze, Yiannis Vasilopoulos, Efterpi Zafiriou, Aikaterini Patsatsi, Costas Stamatis, Polyxeni Gidarokosta, Dimitrios Sotiriadis, Theologia Sarafidou, Zissis Mamuris
Netherton syndrome (OMIM #256500) is a rare but severe autosomal recessive form of ichthyosis that affects the skin, hair, and immune system. The identification of SPINK5, which encodes for the serine protease inhibitor LEKTI, as the gene responsible for Netherton syndrome, enabled the search for causative mutations in Netherton syndrome patients and families. However, information regarding these mutations and their association with the pathological Netherton syndrome phenotype is scarce. Herein, we provide an up-to-date overview of 80 different mutations in exonic as well as intronic regions that have been currently identified in 172 homozygous or compound heterozygous patients from 144 families...
November 30, 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27899669/an-ultraconserved-element-uce-controls-homeostatic-splicing-of-arglu1-mrna
#8
Stephan P Pirnie, Ahmad Osman, Yinzhou Zhu, Gordon G Carmichael
Arginine and Glutamate-Rich protein 1 (ARGLU1) is a protein whose function is poorly understood, but may act in both transcription and pre-mRNA splicing. We demonstrate that the ARGLU1 gene expresses at least three distinct RNA splice isoforms - a fully spliced isoform coding for the protein, an isoform containing a retained intron that is detained in the nucleus, and an isoform containing an alternative exon that targets the transcript for nonsense mediated decay. Furthermore, ARGLU1 contains a long, highly evolutionarily conserved sequence known as an Ultraconserved Element (UCE) that is within the retained intron and overlaps the alternative exon...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899647/spliceosomal-protein-eftud2-mutation-leads-to-p53-dependent-apoptosis-in-zebrafish-neural-progenitors
#9
Lei Lei, Shou-Yu Yan, Ran Yang, Jia-Yu Chen, Yumei Li, Ye Bu, Nannan Chang, Qinchao Zhou, Xiaojun Zhu, Chuan-Yun Li, Jing-Wei Xiong
Haploinsufficiency of EFTUD2 (Elongation Factor Tu GTP Binding Domain Containing 2) is linked to human mandibulofacial dysostosis, Guion-Almeida type (MFDGA), but the underlying cellular and molecular mechanisms remain to be addressed. We report here the isolation, cloning and functional analysis of the mutated eftud2 (snu114) in a novel neuronal mutant fn10a in zebrafish. This mutant displayed abnormal brain development with evident neuronal apoptosis while the development of other organs appeared less affected...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899591/modulation-of-nonsense-mediated-decay-by-rapamycin
#10
Rocio T Martinez-Nunez, Andrew Wallace, Doyle Coyne, Linnea Jansson, Miles Rush, Hanane Ennajdaoui, Sol Katzman, Joanne Bailey, Katrin Deinhardt, Tilman Sanchez-Elsner, Jeremy R Sanford
Rapamycin is a naturally occurring macrolide whose target is at the core of nutrient and stress regulation in a wide range of species. Despite well-established roles as an inhibitor of cap-dependent mRNA translation, relatively little is known about its effects on other modes of RNA processing. Here, we characterize the landscape of rapamycin-induced post-transcriptional gene regulation. Transcriptome analysis of rapamycin-treated cells reveals genome-wide changes in alternative mRNA splicing and pronounced changes in NMD-sensitive isoforms...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27886048/interactions-between-the-hiv-1-unspliced-mrna-and-host-mrna-decay-machineries
#11
REVIEW
Daniela Toro-Ascuy, Bárbara Rojas-Araya, Fernando Valiente-Echeverría, Ricardo Soto-Rifo
The human immunodeficiency virus type-1 (HIV-1) unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation...
November 23, 2016: Viruses
https://www.readbyqxmd.com/read/27875971/therapeutic-suppression-of-nonsense-mutation-an-emerging-target-in-multiple-diseases-and-thrombotic-disorders
#12
Md Asiful Islam, Fahmida Alam, Mohammad Amjad Kamal, Siew Hua Gan, Kah Keng Wong, Teguh Haryo Sasongko
Nonsense mutations contribute to approximately 10-30% of the total human inherited diseases via disruption of protein translation. If any of the three termination codons (UGA, UAG and UAA) emerges prematurely [known as premature termination codon (PTC)] before the natural canonical stop codon, truncated non-functional proteins or proteins with deleterious loss or gain-of-function activities are synthesized, followed by the development of nonsense mutation-mediated diseases. In the past decade, PTC-associated diseases captured much attention in biomedical research, especially as molecular therapeutic targets via nonsense suppression (i...
November 22, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27874031/harnessing-short-poly-a-binding-protein-interacting-peptides-for-the-suppression-of-nonsense-mediated-mrna-decay
#13
Tobias Fatscher, Niels H Gehring
Nonsense-mediated mRNA decay (NMD) is a cellular process that eliminates messenger RNA (mRNA) substrates with premature translation termination codons (PTCs). In addition, NMD regulates the expression of a number of physiological mRNAs, for example transcripts containing long 3' UTRs. Current models implicate the interaction between cytoplasmic poly(A)-binding protein (PABPC1) and translation termination in NMD. Accordingly, PABPC1 present within close proximity of a termination codon antagonizes NMD. Here, we use reporter mRNAs with different NMD-inducing 3' UTRs to establish a general NMD-inhibiting property of PABPC1...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872583/ablation-of-sphingosine-1-phosphate-receptor-subtype-3-impairs-hippocampal-neuron-excitability-in-vitro-and-spatial-working-memory-in-vivo
#14
Daniela Weth-Malsch, Michiel Langeslag, Dimitra Beroukas, Luca Zangrandi, Iris Kastenberger, Serena Quarta, Philipp Malsch, Theodora Kalpachidou, Christoph Schwarzer, Richard L Proia, Rainer V Haberberger, Michaela Kress
Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate (S1P) within the central nervous system has recently gained more and more attention, as it has been connected to major diseases such as multiple sclerosis and Alzheimer's disease. Even though much data about the functions of the five S1P receptors has been collected for other organ systems, we still lack a complete understanding for their specific roles, in particular within the brain. Therefore, it was the aim of this study to further elucidate the role of S1P receptor subtype 3 (S1P3) in vivo and in vitro with a special focus on the hippocampus...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27864472/transcriptome-wide-identification-of-nmd-targeted-human-mrnas-reveals-extensive-redundancy-between-smg6-and-smg7-mediated-degradation-pathways
#15
Martino Colombo, Evangelos D Karousis, Joël Bourquin, Rémy Bruggmann, Oliver Mühlemann
Besides degrading aberrant mRNAs that harbor a premature translation termination codon (PTC), nonsense-mediated mRNA decay (NMD) also targets many seemingly "normal" mRNAs that encode for full-length proteins. To identify a bona fide set of such endogenous NMD targets in human cells, we applied a meta-analysis approach in which we combined transcriptome profiling of knockdowns and rescues of the three NMD factors UPF1, SMG6 and SMG7. We provide evidence that this combinatorial approach identifies NMD-targeted transcripts more reliably than previous attempts that focused on inactivation of single NMD factors...
November 18, 2016: RNA
https://www.readbyqxmd.com/read/27864101/targeted-exome-sequencing-identifies-novel-compound-heterozygous-mutations-in-p3h1-in-a-fetus-with-osteogenesis-imperfecta-type-viii
#16
Yanru Huang, Libin Mei, Weigang Lv, Haoxian Li, Rui Zhang, Qian Pan, Hu Tan, Jing Guo, Xiaomei Luo, Chen Chen, Desheng Liang, Lingqian Wu
Osteogenesis imperfecta (OI) is a highly clinically and genetically heterogeneous group of disorders. It is difficult to identify severe OI in the perinatal period. Here, a Chinese woman with a suspected history of fetal OI was referred to our institution at 19weeks of gestation, due to ultrasound inspection during antenatal screening, which revealed bulbous metaphyses, short humeri, and short thick bent femora in the fetus. Using targeted exome sequencing of 248 genes known to be involved in skeletal system diseases, we identified novel compound heterozygous mutation in the P3H1 gene in the fetus with OI type VIII: c...
November 15, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27861119/splicing-repression-allows-the-gradual-emergence-of-new-alu-exons-in-primate-evolution
#17
Jan Attig, Igor Ruiz de Los Mozos, Nejc Haberman, Zhen Wang, Warren Emmett, Kathi Zarnack, Julian König, Jernej Ule
Alu elements are retrotransposons that frequently form new exons during primate evolution. Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exons. We identify 3100 new Alu-exons and show that NMD more efficiently recognises transcripts with Alu-exons compared to other exons with premature termination codons. However, some Alu-exons escape NMD, especially when an adjacent intron is retained, highlighting the importance of concerted repression by splicing and NMD...
November 18, 2016: ELife
https://www.readbyqxmd.com/read/27855198/identification-and-characterization-of-a-new-protein-isoform-of-human-5-lipoxygenase
#18
Ann-Kathrin Häfner, Kim Beilstein, Philipp Graab, Ann-Katrin Ball, Meike J Saul, Bettina Hofmann, Dieter Steinhilber
Leukotrienes (LTs) are inflammatory mediators that play a pivotal role in many diseases like asthma bronchiale, atherosclerosis and in various types of cancer. The key enzyme for generation of LTs is the 5-lipoxygenase (5-LO). Here, we present a novel putative protein isoform of human 5-LO that lacks exon 4, termed 5-LOΔ4, identified in cells of lymphoid origin, namely the Burkitt lymphoma cell lines Raji and BL41 as well as primary B and T cells. Deletion of exon 4 does not shift the reading frame and therefore the mRNA is not subjected to non-mediated mRNA decay (NMD)...
2016: PloS One
https://www.readbyqxmd.com/read/27853137/cug-binding-protein-1-regulates-hsc-activation-and-liver-fibrogenesis
#19
Xingxin Wu, Xudong Wu, Yuxiang Ma, Fenli Shao, Yang Tan, Tao Tan, Liyun Gu, Yang Zhou, Beicheng Sun, Yang Sun, Xuefeng Wu, Qiang Xu
Excessive activation of hepatic stellate cells (HSCs) is a key step in liver fibrogenesis. Here we report that CUG-binding protein 1 (CUGBP1) expression is elevated in HSCs and positively correlates with liver fibrosis severity in human liver biopsies. Transforming growth factor-beta (TGF-β) selectively increases CUGBP1 expression in cultured HSCs in a p38 mitogen-activated protein kinase (MAPK)-dependent manner. Knockdown of CUGBP1 inhibits alpha smooth muscle actin (α-SMA) expression and promotes interferon gamma (IFN-γ) production in HSCs in vitro...
November 17, 2016: Nature Communications
https://www.readbyqxmd.com/read/27851888/regulation-of-heat-inducible-hspa1a-gene-expression-during-maternal-to-embryo-transition-and-in-response-to-heat-in-in-vitro-produced-bovine-embryos
#20
Jean-Marc Lelièvre, Nathalie Peynot, Sylvie Ruffini, Ludivine Laffont, Daniel Le Bourhis, Pierre-Marie Girard, Véronique Duranthon
In in vitro-produced (IVP) bovine embryos, a burst in transcriptional activation of the embryonic genome (EGA) occurs at the 8-16-cell stage. To examine transcriptional regulation prior to EGA, notably in response to heat stress, we asked (1) whether the spontaneous expression of a luciferase transgene that is driven by the minimal mouse heat-shock protein 1b (hspa1b) gene promoter paralleled that of HSPA1A during EGA in IVP bovine embryo and (2) whether expression of the endogenous heat-inducible iHSPA group member HSPA1A gene and the hspa1b/luciferase transgene were induced by heat stress (HS) prior to EGA...
November 17, 2016: Reproduction, Fertility, and Development
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