近日，中科院上海生命科學研究院/上海交通大學醫學院健康科學研究所分子遺傳（孔祥銀）課題組博士生張振國等人發現RNA剪接噪音是導致細胞內豐富提前終止密碼子形成的重要原因。該成果在線發表在BMC Biology雜誌上。
高等生物細胞內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可以被無義介導的mRNA降解機制降解。問題是細胞為什麼要產生大量註定要被無義介導的mRNA降解機制降解的mRNA? 一個模型是基因轉錄、RNA剪接具有不可避免的高噪音(Splicing noise)，雜散轉錄產物是常見的。這些雜散轉錄產物很可能是有害的。為防止高成本的翻譯，他們必須被清除。另一個模型是在某些情況下， 如環境脅迫，無義介導的mRNA降解是可以被調節的;通過抑制無義介導的mRNA降解，可以上調含有提前終止密碼子mRNA的豐度。
孔祥銀課題組與英國巴斯大學Hurst教授合作，通過對人和小鼠轉錄組的系統研究，發現細胞內豐富提前終止密碼子主要是由於RNA剪切噪音產生，支持Splicing noise模型。但是，古老外顯子上的提前終止密碼子，通過與無義介導的mRNA降解配合, 調節基因翻譯，是一個更合理的解釋。
該項工作得到了國家科技部、國家自然科學基金委和中科院項目的支持。（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.