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https://www.readbyqxmd.com/read/28077491/sphingosine-1-phosphate-lyase-deficiency-causes-charcot-marie-tooth-neuropathy
#1
Derek Atkinson, Jelena Nikodinovic Glumac, Bob Asselbergh, Biljana Ermanoska, David Blocquel, Regula Steiner, Alejandro Estrada-Cuzcano, Kristien Peeters, Tinne Ooms, Els De Vriendt, Xiang-Lei Yang, Thorsten Hornemann, Vedrana Milic Rasic, Albena Jordanova
OBJECTIVE: To identify the unknown genetic cause in a nuclear family with an axonal form of peripheral neuropathy and atypical disease course. METHODS: Detailed neurologic, electrophysiologic, and neuropathologic examinations of the patients were performed. Whole exome sequencing of both affected individuals was done. The effect of the identified sequence variations was investigated at cDNA and protein level in patient-derived lymphoblasts. The plasma sphingoid base profile was analyzed...
January 11, 2017: Neurology
https://www.readbyqxmd.com/read/28062855/expression-of-the-erf1-translation-termination-factor-is-controlled-by-an-autoregulatory-circuit-involving-readthrough-and-nonsense-mediated-decay-in-plants
#2
Tünde Nyikó, Andor Auber, Levente Szabadkai, Anna Benkovics, Mariann Auth, Zsuzsanna Mérai, Zoltán Kerényi, Andrea Dinnyés, Ferenc Nagy, Dániel Silhavy
When a ribosome reaches a stop codon, the eukaryotic Release Factor 1 (eRF1) binds to the A site of the ribosome and terminates translation. In yeasts and plants, both over- and underexpression of eRF1 lead to altered phenotype indicating that eRF1 expression should be strictly controlled. However, regulation of eRF1 level is still poorly understood. Here we show that expression of plant eRF1 is controlled by a complex negative autoregulatory circuit, which is based on the unique features of the 3'untranslated region (3'UTR) of the eRF1-1 transcript...
January 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28059081/aba-unresponsive-snrk2-protein-kinases-regulate-mrna-decay-under-osmotic-stress-in-plants
#3
Fumiyuki Soma, Junro Mogami, Takuya Yoshida, Midori Abekura, Fuminori Takahashi, Satoshi Kidokoro, Junya Mizoi, Kazuo Shinozaki, Kazuko Yamaguchi-Shinozaki
Rapid changes in messenger RNA population are vital for plants to properly exert multiple adaptive responses under continuously changing stress conditions. Transcriptional activation mediated by the 'abscisic acid (ABA)-activated SnRK2 protein kinases-ABA-responsive element (ABRE)-binding proteins/ABRE-binding factors (AREB/ABFs)' signalling module is a crucial step in the expression of stress-inducible genes under osmotic stress conditions in Arabidopsis(1-4). In addition to transcriptional control, proper transcript levels of individual genes can be achieved by post-transcriptional regulation, but how this regulation functions under stress conditions and the underlying molecular mechanisms remain elusive...
January 6, 2017: Nature Plants
https://www.readbyqxmd.com/read/28054965/attacked-from-all-sides-rna-decay-in-antiviral-defense
#4
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/28054750/somatic-med12-nonsense-mutation-escapes-mrna-decay-and-reveals-a-motif-required-for-nuclear-entry
#5
Tuomas Heikkinen, Kati Kämpjärvi, Salla Keskitalo, Pernilla von Nandelstadh, Xiaonan Liu, Ville Rantanen, Esa Pitkänen, Matias Kinnunen, Heikki Kuusanmäki, Mika Kontro, Mikko Turunen, Netta Mäkinen, Jussi Taipale, Caroline Heckman, Kaisa Lehti, Satu Mustjoki, Markku Varjosalo, Pia Vahteristo
MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, breast tumors, and chronic lymphocytic leukemia. Here, we characterize the first MED12 5' end nonsense mutation (c.97G>T, p.E33X) identified in acute lymphoblastic leukemia and show that it escapes nonsense-mediated mRNA decay (NMD) by using an alternative translation initiation site. The resulting N-terminally truncated protein is unable to enter the nucleus due to the lack of identified nuclear localization signal (NLS)...
January 5, 2017: Human Mutation
https://www.readbyqxmd.com/read/28045588/global-decay-of-mrna-is-a-hallmark-of-apoptosis-in-aging-xenopus-eggs
#6
Alexander A Tokmakov, Sho Iguchi, Tetsushi Iwasaki, Yasuo Fukami, Ken-Ichi Sato
Cytoplasmic mRNAs are specifically degraded in somatic cells as a part of early apoptotic response. However, no reports have been presented so far concerning mRNA fate in apoptotic gametes. In the present study, we analyzed the content of various cytoplasmic mRNAs in aging oocytes and eggs of the African clawed frog, Xenopus laevis. To circumvent large gene expression variation among the individual oocytes and eggs, single-cell monitoring of transcript levels has been implemented, using multiple cytoplasmic collections and reverse transcriptase quantitative PCR...
January 3, 2017: RNA Biology
https://www.readbyqxmd.com/read/28027311/somatic-mutation-patterns-in-hemizygous-genomic-regions-unveil-purifying-selection-during-tumor-evolution
#7
Jimmy Van den Eynden, Swaraj Basu, Erik Larsson
Identification of cancer driver genes using somatic mutation patterns indicative of positive selection has become a major goal in cancer genomics. However, cancer cells additionally depend on a large number of genes involved in basic cellular processes. While such genes should in theory be subject to strong purifying (negative) selection against damaging somatic mutations, these patterns have been elusive and purifying selection remains inadequately explored in cancer. Here, we hypothesized that purifying selection should be evident in hemizygous genomic regions, where damaging mutations cannot be compensated for by healthy alleles...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/28017590/fluorescence-amplification-method-for-forward-genetic-discovery-of-factors-in-human-mrna-degradation
#8
Andrei Alexandrov, Mei-Di Shu, Joan A Steitz
Nonsense-mediated decay (NMD) degrades mRNAs containing a premature termination codon (PTC). PTCs are a frequent cause of human genetic diseases, and the NMD pathway is known to modulate disease severity. Since partial NMD attenuation can potentially enhance nonsense suppression therapies, better definition of human-specific NMD is required. However, the majority of NMD factors were first discovered in model organisms and then subsequently identified by homology in human. Sensitivity and throughput limitations of existing approaches have hindered systematic forward genetic screening for NMD factors in human cells...
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28013048/pou1f1-the-key-transcription-factor-related-to-somatic-growth-in-tilapia-orechromis-niloticus-is-regulated-by-two-independent-post-transcriptional-regulation-mechanisms
#9
Dongfang Wang, Jingkai Qin, Jirong Jia, Peipei Yan, Wensheng Li
This study aims to determine the post-transcriptional regulation mechanism of the transcription factor pou1f1 (pou class 1 homeobox 1), which is the key gene for pituitary development, somatic growth in vertebrates, and transcription of several hormone genes in teleost fish. MicroRNA miR-223-3p was identified as a bona fide target of pou1f; overexpression of miR-223-3p in primary pituitary cells led to the down-regulation of pou1f1 and downstream genes, and inhibition of miR-223-3p led to the up-regulation of pou1f1 in Nile tilapia dispersed primary pituitary cells...
December 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28011629/a-feedback-mechanism-between-phospholipase-d-and-deadenylase-parn-for-the-shortening-of-eukaryotic-poly-a-mrna-tails-that-is-deregulated-in-cancer-cells
#10
Taylor E Miller, Julian Gomez-Cambronero
The removal of mRNA transcripts poly(A) tails by 3-5 exonucleases is the rate-limiting step in mRNA decay in eukaryotes. Known cellular deadenylases are, the CCR4-NOT and PAN complexes, and poly(A)-specific ribonuclease (PARN). The physiological roles and regulation for PARN is beginning to be elucidated. Since phospholipase D (PLD2 isoform) gene expression is upregulated in breast cancer cells and PARN is downregulated, we examined whether a signaling connection existed between these two enzymes. Silencing PARN with siRNA led to an increase in PLD2 protein and overexpression of PARN did the opposite...
December 23, 2016: Biology Open
https://www.readbyqxmd.com/read/28011423/mrna-decay-in-plants-both-quantity-and-quality-matter
#11
REVIEW
Xinyan Zhang, Hongwei Guo
In eukaryotes, degradation of messenger RNAs (mRNAs) is required for both mRNA quantity and quality control. Fine-tuning of the abundance of mRNAs that are to be translated can be achieved through a deadenylation-mediated RNA decay pathway involving progressive removal of poly(A) tails, decapping and exoribonuclease digestion. While the classical view assumes that mRNAs are degraded only after their exit from protein translation, recent studies have revealed mRNA decay can occur during translation in plants...
December 20, 2016: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28009841/use-of-cellular-decapping-activators-by-positive-strand-rna-viruses
#12
REVIEW
Jennifer Jungfleisch, Bernat Blasco-Moreno, Juana Díez
Positive-strand RNA viruses have evolved multiple strategies to not only circumvent the hostile decay machinery but to trick it into being a priceless collaborator supporting viral RNA translation and replication. In this review, we describe the versatile interaction of positive-strand RNA viruses and the 5'-3' mRNA decay machinery with a focus on the viral subversion of decapping activators. This highly conserved viral trickery is exemplified with the plant Brome mosaic virus, the animal Flock house virus and the human hepatitis C virus...
December 21, 2016: Viruses
https://www.readbyqxmd.com/read/28008922/atp-hydrolysis-by-upf1-is-required-for-efficient-translation-termination-at-premature-stop-codons
#13
Lucas D Serdar, DaJuan L Whiteside, Kristian E Baker
Nonsense-mediated mRNA decay (NMD) represents a eukaryotic quality control pathway that recognizes and rapidly degrades transcripts harbouring nonsense mutations to limit accumulation of non-functional and potentially toxic truncated polypeptides. A critical component of the NMD machinery is UPF1, an RNA helicase whose ATPase activity is essential for NMD, but for which the precise function and site of action remain unclear. We provide evidence that ATP hydrolysis by UPF1 is required for efficient translation termination and ribosome release at a premature termination codon...
December 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/28008748/tbk1-mutation-spectrum-in-an-extended-european-patient-cohort-with-frontotemporal-dementia-and-amyotrophic-lateral-sclerosis
#14
Julie van der Zee, Ilse Gijselinck, Sara Van Mossevelde, Federica Perrone, Lubina Dillen, Bavo Heeman, Veerle Bäumer, Sebastiaan Engelborghs, Jan De Bleecker, Jonathan Baets, Ellen Gelpi, Ricardo Rojas-García, Jordi Clarimón, Alberto Lleó, Janine Diehl-Schmid, Panagiotis Alexopoulos, Robert Perneczky, Matthis Synofzik, Jennifer Just, Ludger Schöls, Caroline Graff, Håkan Thonberg, Barbara Borroni, Alessandro Padovani, Albena Jordanova, Stayko Sarafov, Ivailo Tournev, Alexandre de Mendonça, Gabriel Miltenberger-Miltényi, Frederico Simões do Couto, Alfredo Ramirez, Frank Jessen, Michael T Heneka, Estrella Gómez-Tortosa, Adrian Danek, Patrick Cras, Rik Vandenberghe, Peter De Jonghe, Peter P De Deyn, Kristel Sleegers, Marc Cruts, Christine Van Broeckhoven
We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2538 patients with FTD, ALS or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1...
December 23, 2016: Human Mutation
https://www.readbyqxmd.com/read/28008720/the-exon-junction-complex-a-lifelong-guardian-of-mrna-fate
#15
REVIEW
Lauren A Woodward, Justin W Mabin, Pooja Gangras, Guramrit Singh
During messenger RNA (mRNA) biogenesis and processing in the nucleus, many proteins are imprinted on mRNAs assembling them into messenger ribonucleoproteins (mRNPs). Some of these proteins remain stably bound within mRNPs and have a long-lasting impact on their fate. One of the best-studied examples is the exon junction complex (EJC), a multiprotein complex deposited primarily 24 nucleotides upstream of exon-exon junctions as a consequence of pre-mRNA splicing. The EJC maintains a stable, sequence-independent, hold on the mRNA until its removal during translation in the cytoplasm...
December 23, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27999393/diverse-strategies-used-by-picornaviruses-to-escape-host-rna-decay-pathways
#16
REVIEW
Wendy Ullmer, Bert L Semler
To successfully replicate, viruses protect their genomic material from degradation by the host cell. RNA viruses must contend with numerous destabilizing host cell processes including mRNA decay pathways and viral RNA (vRNA) degradation resulting from the antiviral response. Members of the Picornaviridae family of small RNA viruses have evolved numerous diverse strategies to evade RNA decay, including incorporation of stabilizing elements into vRNA and re-purposing host stability factors. Viral proteins are deployed to disrupt and inhibit components of the decay machinery and to redirect decay machinery to the advantage of the virus...
December 20, 2016: Viruses
https://www.readbyqxmd.com/read/27992413/genome-wide-association-study-of-primary-sclerosing-cholangitis-identifies-new-risk-loci-and-quantifies-the-genetic-relationship-with-inflammatory-bowel-disease
#17
Sun-Gou Ji, Brian D Juran, Sören Mucha, Trine Folseraas, Luke Jostins, Espen Melum, Natsuhiko Kumasaka, Elizabeth J Atkinson, Erik M Schlicht, Jimmy Z Liu, Tejas Shah, Javier Gutierrez-Achury, Kirsten M Boberg, Annika Bergquist, Severine Vermeire, Bertus Eksteen, Peter R Durie, Martti Farkkila, Tobias Müller, Christoph Schramm, Martina Sterneck, Tobias J Weismüller, Daniel N Gotthardt, David Ellinghaus, Felix Braun, Andreas Teufel, Mattias Laudes, Wolfgang Lieb, Gunnar Jacobs, Ulrich Beuers, Rinse K Weersma, Cisca Wijmenga, Hanns-Ulrich Marschall, Piotr Milkiewicz, Albert Pares, Kimmo Kontula, Olivier Chazouillères, Pietro Invernizzi, Elizabeth Goode, Kelly Spiess, Carmel Moore, Jennifer Sambrook, Willem H Ouwehand, David J Roberts, John Danesh, Annarosa Floreani, Aliya F Gulamhusein, John E Eaton, Stefan Schreiber, Catalina Coltescu, Christopher L Bowlus, Velimir A Luketic, Joseph A Odin, Kapil B Chopra, Kris V Kowdley, Naga Chalasani, Michael P Manns, Brijesh Srivastava, George Mells, Richard N Sandford, Graeme Alexander, Daniel J Gaffney, Roger W Chapman, Gideon M Hirschfield, Mariza de Andrade, Simon M Rushbrook, Andre Franke, Tom H Karlsen, Konstantinos N Lazaridis, Carl A Anderson
Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A...
December 19, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27991510/rna-decay-nobody-binds-to-mrna-decapping-proteins
#18
Kim Baumann
No abstract text is available yet for this article.
December 19, 2016: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/27990022/rna-binding-proteins-in-immune-regulation-a-focus-on-ccch-zinc-finger-proteins
#19
Mingui Fu, Perry J Blackshear
Nearly 60 CCCH zinc finger proteins have been identified in humans and mice. These proteins are involved in the regulation of multiple steps of RNA metabolism, including mRNA splicing, polyadenylation, transportation, translation and decay. Several CCCH zinc finger proteins, such as tristetraprolin (TTP), roquin 1 and MCPIP1 (also known as regnase 1), are crucial for many aspects of immune regulation by targeting mRNAs for degradation and modulation of signalling pathways. In this Review, we focus on the emerging roles of CCCH zinc finger proteins in the regulation of immune responses through their effects on cytokine production, immune cell activation and immune homeostasis...
December 19, 2016: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/27989637/reciprocal-regulation-of-acetyl-coa-carboxylase-1-and-senescence-in-human-fibroblasts-involves-oxidant-mediated-p38-mapk-activation
#20
Inés Marmisolle, Jennyfer Martínez, Jie Liu, Mauricio Mastrogiovanni, María M Fergusson, Ilsa I Rovira, Laura Castro, Andrés Trostchansky, María Moreno, Liu Cao, Toren Finkel, Celia Quijano
We sought to explore the fate of the fatty acid synthesis pathway in human fibroblasts exposed to DNA damaging agents capable of inducing senescence, a state of irreversible growth arrest. Induction of premature senescence by doxorubicin or hydrogen peroxide led to a decrease in protein and mRNA levels of acetyl-CoA carboxylase 1 (ACC1), the enzyme that catalyzes the rate-limiting step in fatty-acid biosynthesis. ACC1 decay accompanied the activation of the DNA damage response (DDR), and resulted in decreased lipid synthesis...
October 27, 2016: Archives of Biochemistry and Biophysics
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