生物谷：來自Pennsylvania大學醫(yī)學院的科學家發(fā)現了一種探測并選擇性去除紅細胞中有缺陷的信使RNA的分子機制。其它類似機制存在于多種細胞中,。了解這類系統(tǒng)能幫助我們更好了解遺傳性疾病,，例如地中海型貧血癥。
結果發(fā)表在最新的Nature Structural and Molecular Biology上,。
細胞利用這種監(jiān)視機制來找到并破壞異常RNA,。RNA編譯成蛋白時的錯誤會產生異常的蛋白，這最終導致細胞功能異常甚至死亡,。
Penn小組研究的地中海型貧血由于基因變異引起,，這使得細胞核糖體產生的蛋白質過長。而地中海型貧血表現為血色素蛋白產生數量不足——這是血液中攜帶氧氣的分子,。小組分析的變異是一種在東南亞有數百萬人攜帶的基因,，它是導致胎兒死亡和成年疾病的主要原因。
在過去數年間科學家已經找到了數個監(jiān)視機制,，它們負責識別RNA的特定變異,。例如最常見的一種機制識別無義突變，這會導致RNA產生過短的蛋白,。無義突變能導致肌無力和囊腫纖維化等疾病,。
主要作者之一Stephen A. Liebhaber表示：“我們描述了針對只在紅細胞中存在的RNA的監(jiān)視路徑。”而第一作者Jian Kong說：“這種機制在組織水平被調控,，并同時存在于其它高度分化的細胞中,。了解這一機制能幫助我們更好了解多種基因異常。”
Liebhaber希望進一步研究這種監(jiān)視機制來分析為何它只針對紅細胞,，這類信息能幫助尋找操控這些系統(tǒng)來治療多種紅細胞疾病的方法,。 （劉樂譯自www.physorg.com ）
??原文鏈接http://www.physorg.com/news105200398.html
原始出處:
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 [email protected]
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.
