生物谷：来自Pennsylvania大学医学院的科学家发现了一种探测并选择性去除红细胞中有缺陷的信使RNA的分子机制。其它类似机制存在于多种细胞中。了解这类系统能帮助我们更好了解遗传性疾病，例如地中海型贫血症。
结果发表在最新的Nature Structural and Molecular Biology上。
细胞利用这种监视机制来找到并破坏异常RNA。RNA编译成蛋白时的错误会产生异常的蛋白，这最终导致细胞功能异常甚至死亡。
Penn小组研究的地中海型贫血由于基因变异引起，这使得细胞核糖体产生的蛋白质过长。而地中海型贫血表现为血色素蛋白产生数量不足——这是血液中携带氧气的分子。小组分析的变异是一种在东南亚有数百万人携带的基因，它是导致胎儿死亡和成年疾病的主要原因。
在过去数年间科学家已经找到了数个监视机制，它们负责识别RNA的特定变异。例如最常见的一种机制识别无义突变，这会导致RNA产生过短的蛋白。无义突变能导致肌无力和囊肿纤维化等疾病。
主要作者之一Stephen A. Liebhaber表示：“我们描述了针对只在红细胞中存在的RNA的监视路径。”而第一作者Jian Kong说：“这种机制在组织水平被调控，并同时存在于其它高度分化的细胞中。了解这一机制能帮助我们更好了解多种基因异常。”
Liebhaber希望进一步研究这种监视机制来分析为何它只针对红细胞，这类信息能帮助寻找操控这些系统来治疗多种红细胞疾病的方法。 （刘乐译自www.physorg.com ）
??原文链接http://www.physorg.com/news105200398.html
原始出处:
Nature Structural & Molecular Biology - 14, 670 - 676 (2007)
Published online: 17 June 2007; | doi:10.1038/nsmb1256
A cell type–restricted mRNA surveillance pathway triggered by ribosome extension into the 3' untranslated region
Jian Kong & Stephen A Liebhaber
Department of Genetics and Department of Medicine, University of Pennsylvania School of Medicine, 415 Curie Blvd., CRB 430, Philadelphia, Pennsylvania 19104, USA.
Correspondence should be addressed to Stephen A Liebhaber liebhabe@mail.med.upenn.edu
The accuracy of eukaryotic gene expression is monitored at multiple levels. Surveillance pathways have been identified that degrade messenger RNAs containing nonsense mutations, harboring stalled ribosomes or lacking termination codons. Here we report a previously uncharacterized surveillance pathway triggered by ribosome extension into the 3' untranslated region. This ribosome extension–mediated decay, REMD, accounts for marked repression of protein synthesis from a human -globin gene containing a prevalent antitermination mutation. REMD can be mechanistically distinguished from other surveillance pathways by its functional linkage to accelerated deadenylation, by its independence from the NMD factor Upf1 and by cell-type restriction. This unusual pathway of mRNA surveillance is likely to act as a modifier of additional genetic defects and may reflect post-transcriptional controls particular to erythroid and other differentiated cell lineages.
