Global analysis of mRNA isoform half-lives reveals stabilizing and destabilizing elements in yeast.
Global analysis of mRNA isoform half-lives reveals stabilizing and destabilizing elements in yeast.
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DOI：
10.1016/j.cell.2013.12.026
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发表时间：
2014-02-13
期刊：
影响因子：
64.5
通讯作者：
Struhl K
中科院分区：
文献类型：
--
作者：
Geisberg JV;Moqtaderi Z;Fan X;Ozsolak F;Struhl K
我们通过快速消耗细胞核中的RNA聚合酶II并在整个衰变过程中进行直接RNA测序，测量了酵母中21，248种mRNA 3 ′亚型的半衰期。有趣的是，来自同一基因的mRNA同种型（包括几乎相同的同种型）的半衰期通常差异很大。基于具有不同半衰期的异构体簇，我们确定了数百个序列，这些序列在mRNA终止于下游时赋予稳定性或不稳定性。一类稳定元件是polyU序列，其可以与poly（A）尾相互作用，抑制poly（A）结合蛋白的缔合，并在引入异位转录物时赋予增加的稳定性。更一般地，去稳定化和稳定化元件与poly（A）尾接合双链结构的倾向有关。被工程化以折叠成不涉及poly（A）尾的3 ′茎环结构的同种型表现出甚至更长的半衰期。我们认为3 ′端的双链结构是mRNA稳定性的主要决定因素。
We measured half-lives of 21,248 mRNA 3′ isoforms in yeast by rapidly depleting RNA polymerase II from the nucleus and performing direct RNA sequencing throughout the decay process. Interestingly, half-lives of mRNA isoforms from the same gene, including nearly identical isoforms, often vary widely. Based on clusters of isoforms with different half-lives, we identify hundreds of sequences conferring stabilization or destabilization upon mRNAs terminating downstream. One class of stabilizing element is a polyU sequence that can interact with poly(A) tails, inhibit the association of poly(A)-binding protein, and confer increased stability upon introduction into ectopic transcripts. More generally, destabilizing and stabilizing elements are linked to the propensity of the poly(A) tail to engage in double-stranded structures. Isoforms engineered to fold into 3′ stem-loop structures not involving the poly(A) tail exhibit even longer half-lives. We suggest that double-stranded structures at 3′ ends are a major determinant of mRNA stability.
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