共查询到20条相似文献,搜索用时 31 毫秒
1.
2.
3.
Mutations in SNRPB,Encoding Components of the Core Splicing Machinery,Cause Cerebro‐Costo‐Mandibular Syndrome 下载免费PDF全文
Séverine Bacrot Mathilde Doyard Céline Huber Olivier Alibeu Niklas Feldhahn Daphné Lehalle Didier Lacombe Sandrine Marlin Patrick Nitschke Florence Petit Marie‐Paule Vazquez Arnold Munnich Valérie Cormier‐Daire 《Human mutation》2015,36(2):187-190
4.
5.
Somatic MED12 Nonsense Mutation Escapes mRNA Decay and Reveals a Motif Required for Nuclear Entry 下载免费PDF全文
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 《Human mutation》2017,38(3):269-274
6.
7.
8.
9.
Akio Yamashita 《Genes to cells : devoted to molecular & cellular mechanisms》2013,18(3):161-175
SMG‐1, a member of the PIKK (phosphoinositide 3‐kinase‐related kinase) family, plays a critical role in the mRNA quality control system known as nonsense‐mediated mRNA decay (NMD). NMD protects cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) which encode nonfunctional or potentially harmful truncated proteins. SMG‐1 directly phosphorylates Upf1 helicase, another key component of NMD, upon recognition of PTC on postspliced mRNA during the initial round of translation. Phosphorylated‐Upf1 recruits the SMG‐5/SMG‐7 complex to induce ribosome dissociation and decapping‐mediated decay. Phospho‐Upf1 also recruits the SMG‐6 endonuclease which might be involved in endo‐cleavage. Upf1 ATPase/helicase activities are likely required for the activation of other mRNA decay enzymes and the mRNA‐protein complex dissociation to complete NMD. At present, a variety of tools are available that can specifically suppress NMD, and it has become possible to examine the contribution of NMD in a variety of physiological and pathological conditions. 相似文献
10.
11.
12.
Anélia Horvath Jérôme Bertherat Lionel Groussin Marine Guillaud‐Bataille Kitman Tsang Laure Cazabat Rosella Libé Elaine Remmers Fernande René‐Corail Fabio Rueda Faucz Eric Clauser Alain Calender Xavier Bertagna J. Aidan Carney Constantine A. Stratakis 《Human mutation》2010,31(4):369-379
PRKAR1A encodes the regulatory subunit type 1‐alpha (RIα) of the cyclic adenosine monophosphate (cAMP)‐dependent protein kinase (PKA). Inactivating PRKAR1A mutations are known to be responsible for the multiple neoplasia and lentiginosis syndrome Carney complex (CNC). To date, at least 117 pathogenic variants in PRKAR1A have been identified (online database: http://prkar1a.nichd.nih.gov ). The majority are subject to nonsense mediated mRNA decay (NMD), leading to RIα haploinsufficiency and, as a result, activated cAMP signaling. Recently, it became apparent that CNC may be caused not only by RIα haploinsufficiency, but also by the expression of altered RIα protein, as proven by analysis of expressed mutations in the gene, consisting of aminoacid substitutions and in‐frame genetic alterations. In addition, a new subgroup of mutations that potentially escape NMD and result in CNC through altered (rather than missing) protein has been analyzed—these are frame‐shifts in the 3′ end of the coding sequence that shift the stop codon downstream of the normal one. The mutation detection rate in CNC patients is recently estimated at above 60%; PRKAR1A mutation‐negative CNC patients are characterized by significant phenotypic heterogeneity. In this report, we present a comprehensive analysis of all presently known PRKAR1A sequence variations and discuss their molecular context and clinical phenotype. Hum Mutat 31:369–379, 2010. Published 2010 Wiley‐Liss, Inc. 相似文献
13.
Flynn C Zheng S Yan L Hedges L Womack B Fessel J Cogan J Austin E Loyd J West J Zhao Z Hamid R 《American journal of respiratory cell and molecular biology》2012,47(1):20-27
The molecular mechanisms underlying the reduced penetrance seen in the nonsense-mediated decay-positive (NMD+) BMPR2 mutation-associated hereditary pulmonary arterial hypertension (HPAH) remain unknown. We reasoned that the cellular and genetic mechanisms behind this phenomenon could be uncovered by combining expression profiling with Connectivity Map (cMap) analysis. Cultured lymphocytes from 10 patients with HPAH and 10 matched familial control subjects, all with NMD+ BMPR2 mutations, were subjected to expression analysis. For each group, the expression data were combined before analysis. This generated a signature of 23 up-regulated and 12 down-regulated genes in patients with HPAH compared with control subjects (the "PAH penetrance signature"). Although gene set enrichment analysis of this signature was not uniquely informative, cMap analysis identified drugs with expression signatures similar to the PAH penetrance signature. Several of these drugs were predicted to influence reactive oxygen species (ROS) formation. This hypothesis was tested and confirmed in the same cells initially subjected to the expression analysis using quantitative biochemical detection of ROS concentration. We conclude that expression of the PAH penetrance signature represents an increased risk of developing clinical HPAH and that ROS formation may play a role in pathogenesis of HPAH. These results provide the first molecular insights into NMD+ BMPR2 related HPAH penetrance and highlight the potential utility of cMap analyses in pulmonary research. 相似文献
14.
15.
16.
17.
X Xu L Zhang P Tong G Xun W Su Z Xiong T Zhu Y Zheng S Luo Y Pan K Xia Z Hu 《Clinical genetics》2013,83(6):560-564
Mental retardation (MR) is a group of common and complex disabilities affecting the central nervous system and appears before the period of brain developmental maturity. Recently, only 40% of genetic MR has been identified, however 60% remains unexplained. In this study, we applied exome sequencing to identify the mutation p.R430X in UPF3B gene in an MR pedigree, which was validated by Sanger sequencing and completely cosegregated within this family. UPF3B gene encodes a protein involved in nonsense‐mediated mRNA decay (NMD). By real‐time quantitative PCR, we detected the significant difference in the mRNA expression levels of the UPF3B and the classical NMD pathway target growth arrest and DNA‐damage‐inducible‐beta (GADD45B) between the patients and the controls. Our results directly implicated that the mutation p.R430X in UPF3B gene was the genetic etiology of the MR pedigree. 相似文献
18.
Machado RD Aldred MA James V Harrison RE Patel B Schwalbe EC Gruenig E Janssen B Koehler R Seeger W Eickelberg O Olschewski H Elliott CG Glissmeyer E Carlquist J Kim M Torbicki A Fijalkowska A Szewczyk G Parma J Abramowicz MJ Galie N Morisaki H Kyotani S Nakanishi N Morisaki T Humbert M Simonneau G Sitbon O Soubrier F Coulet F Morrell NW Trembath RC 《Human mutation》2006,27(2):121-132
19.
TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis 下载免费PDF全文
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 Silvia Testi 《Human mutation》2017,38(3):297-309