Center for RNA Biology, Ohio State University, Columbus, OH 43210, USA.
Cell Rep. 2012 Sep 27;2(3):674-84. doi: 10.1016/j.celrep.2012.07.011. Epub 2012 Aug 23.
The notion that decapping leads irreversibly to messenger RNA (mRNA) decay was contradicted by the identification of capped transcripts missing portions of their 5' ends and a cytoplasmic complex that can restore the cap on uncapped mRNAs. In this study, we used accumulation of uncapped transcripts in cells inhibited for cytoplasmic capping to identify the targets of this pathway. Inhibition of cytoplasmic capping results in the destabilization of some transcripts and the redistribution of others from polysomes to nontranslating messenger ribonucleoproteins, where they accumulate in an uncapped state. Only a portion of the mRNA transcriptome is affected by cytoplasmic capping, and its targets encode proteins involved in nucleotide binding, RNA and protein localization, and the mitotic cell cycle. The 3' untranslated regions of recapping targets are enriched for AU-rich elements and microRNA binding sites, both of which function in cap-dependent mRNA silencing. These findings identify a cyclical process of decapping and recapping that we term cap homeostasis.
帽结构缺失导致信使 RNA（mRNA）降解的观点与发现的缺少 5' 端部分序列的帽状转录本以及一种能够将非帽状 mRNA 重新加上帽结构的细胞质复合物相矛盾。在本研究中，我们利用抑制细胞质加帽后未加帽转录本的积累，鉴定了该通路的作用靶点。细胞质加帽的抑制会导致一些转录本的不稳定性，并使其他转录本从多核糖体重新分布到非翻译信使核糖核蛋白，在那里它们以未加帽的状态积累。只有一部分 mRNA 转录组受到细胞质加帽的影响，其靶标编码参与核苷酸结合、RNA 和蛋白质定位以及有丝分裂细胞周期的蛋白质。重新加帽靶标的 3' 非翻译区富含 AU 富含元件和 microRNA 结合位点，这两者都在帽依赖的 mRNA 沉默中发挥作用。这些发现确定了一种去帽和加帽的循环过程，我们称之为帽状结构动态平衡。
