近日，中科院上海生命科學(xué)研究院/上海交通大學(xué)醫(yī)學(xué)院健康科學(xué)研究所分子遺傳（孔祥銀）課題組博士生張振國(guó)等人發(fā)現(xiàn)RNA剪接噪音是導(dǎo)致細(xì)胞內(nèi)豐富提前終止密碼子形成的重要原因,。該成果在線發(fā)表在BMC Biology雜志上,。
高等生物細(xì)胞內(nèi)存在大量含有提前終止密碼子的mRNA。含有提前終止密碼子的mRNA可以被無(wú)義介導(dǎo)的mRNA降解機(jī)制降解,。問(wèn)題是細(xì)胞為什么要產(chǎn)生大量注定要被無(wú)義介導(dǎo)的mRNA降解機(jī)制降解的mRNA? 一個(gè)模型是基因轉(zhuǎn)錄,、RNA剪接具有不可避免的高噪音(Splicing noise)，雜散轉(zhuǎn)錄產(chǎn)物是常見(jiàn)的,。這些雜散轉(zhuǎn)錄產(chǎn)物很可能是有害的,。為防止高成本的翻譯，他們必須被清除,。另一個(gè)模型是在某些情況下,， 如環(huán)境脅迫，無(wú)義介導(dǎo)的mRNA降解是可以被調(diào)節(jié)的;通過(guò)抑制無(wú)義介導(dǎo)的mRNA降解,，可以上調(diào)含有提前終止密碼子mRNA的豐度,。
孔祥銀課題組與英國(guó)巴斯大學(xué)Hurst教授合作,，通過(guò)對(duì)人和小鼠轉(zhuǎn)錄組的系統(tǒng)研究，發(fā)現(xiàn)細(xì)胞內(nèi)豐富提前終止密碼子主要是由于RNA剪切噪音產(chǎn)生,，支持Splicing noise模型,。但是，古老外顯子上的提前終止密碼子,，通過(guò)與無(wú)義介導(dǎo)的mRNA降解配合, 調(diào)節(jié)基因翻譯,，是一個(gè)更合理的解釋。
該項(xiàng)工作得到了國(guó)家科技部,、國(guó)家自然科學(xué)基金委和中科院項(xiàng)目的支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
BMC Biol. 2009 May 14;7(1):23.
Noisy splicing, more than expression regulation, explains why some exons are subject to nonsense-mediated mRNA decay.
Zhang Z, Xin D, Wang P, Zhou L, Hu L, Kong X, Hurst LD.
ABSTRACT: BACKGROUND: Nonsense-mediated decay is a mechanism that degrades mRNAs with a premature termination codon. That some exons have premature termination codons at fixation is paradoxical: why make a transcript if it is only to be destroyed? One model supposes that splicing is inherently noisy and spurious transcripts are common. The evolution of a premature termination codon in a regularly made unwanted transcript can be a means to prevent costly translation. Alternatively, nonsense-mediated decay can be regulated under certain conditions so the presence of a premature termination codon can be a means to up-regulate transcripts needed when nonsense-mediated decay is suppressed. RESULTS: To resolve this issue we examined the properties of putative nonsense-mediated decay targets in humans and mice. We started with a well-annotated set of protein coding genes and found that 2 to 4% of genes are probably subject to nonsense-mediated decay, and that the premature termination codon reflects neither rare mutations nor sequencing artefacts. Several lines of evidence suggested that the noisy splice model has considerable relevance: 1) exons that are uniquely found in nonsense-mediated decay transcripts (nonsense-mediated decay-specific exons) tend to be newly created; 2) have low-inclusion level; 3) tend not to be a multiple of three long; 4) belong to genes with multiple splice isoforms more often than expected; and 5) these genes are not obviously enriched for any functional class nor conserved as nonsense-mediated decay candidates in other species. However, nonsense-mediated decay-specific exons for which distant orthologous exons can be found tend to have been under purifying selection, consistent with the regulation model. CONCLUSION: We conclude that for recently evolved exons the noisy splicing model is the better explanation of their properties, while for ancient exons the nonsense-mediated decay regulated gene expression is a viable explanation.
