3'-端尿苷酸化引发RNA降解的机制

RNA Degradation is Induced by 3'-terminal Uridylation

RNA末端的转录后修饰对其稳定性影响较大.最近研究发现,3'-末端无需模板的添加尿苷酸(尿苷酸化),可能是真核生物RNA的一种普遍存在的转录后修饰方式.借此形成的1个RNA降解的分子标记,引发多种RNA降解,如小RNA或其前体、mRNA或mRNA被RNA诱导沉默复合体内切后的上游片段及其组蛋白mRNA等.某些情况下,尿苷酸化的RNA被1种新发现的外切核酸酶Dis3L2特异降解,推测Dis3L2可能代表了真核生物RNA 3'→5'方向独立于外切体之外的一种新的降解途径.此外,尿苷酸化在RNA代谢中可能具有重要的功能,如果发生异常会导致多种人类疾病,如癌症和Perlman综合征等.本文综述了尿苷酸化引发RNA降解的几种方式,有助于进一步了解RNA降解的机制及其生物学意义.

Post-transcriptional modifications of the 3＇-ends of RNAs have a profound impact on their stability. Recently, it has been found that the post-transcriptional non-templated addition of uridines to the 3＇-ends of RNAs （uridylation） is wide spread in multiple eukaryotes, and may produce a molecular decay marker targeting various RNAs for degradation, such as small RNAs or their precursors, mRNAs or their 5＇ fragments produced by RNA-induced silencing complex （RISC） cleavage and histone mRNAs. In certain condition, these uridylated RNAs are selectively decayed by a novel exoribonuclease Dis3L2, which may specify a novel 3＇-5＇ eukaryotic RNA exosome-independent degradation pathway. Due to a central role of uridylation in RNA metabolism, abnormalities of this mechanism may contribute to a variety of human diseases, such as cancer and perlman syndrome. This review mainly concentrates on the various mechanisms of uridylation mediated RNA degradation, it may help readers to deepen the understanding of principles of RNA degradation and its significance of biological function.