选择性多聚腺苷酸化的生物学效应及其调控机制研究进展

Advances of functional consequences and regulation mechanisms of alternative cleavage and polyadenylation

真核生物基因的前体mRNA(pre-mRNA)及一些lncRNA在成熟过程中其3'端会发生剪切和多聚腺苷酸化反应(cleavage and polyadenylation, C/P),C/P的发生需要多聚腺苷酸化信号(polyadenylation signal, PAS)的存在。选择性多聚腺苷酸化(alternative cleavage and polyadenylation, APA)是指具有多个PAS的基因,在其mRNA3'端成熟过程中,由于选择不同的PAS,导致产生出多个3'UTR长度和序列组成不同的转录异构体。3'UTR长度和序列的不同会影响mRNA的稳定性、翻译效率、运输和细胞定位等,因此APA是真核生物的一个重要转录后调控方式。近年来,对大量动物、植物及酵母的基因组测序分析发现,APA在真核生物广泛存在,针对APA的生物学效应和调控机制开展了一系列研究。目前已鉴定出许多APA调控的顺式调控元件和反式作用因子。本文重点介绍了APA生物学效应和调控机制的最新研究进展,并探讨了未来APA调控的研究方向。

During the maturation of pre-mRNAs and some lncRNAs,their 3’ends are cleaved and polyadenylated.The cleavage and polyadenylation(C/P)require the presence of a polyadenylation signal(PAS)at the RNA 3’end.Most eukaryotic genes have multiple PASs,resulting in alternative cleavage and polyadenylation(APA).APA leads to transcript isoforms with different coding potentials and/or variable 3’UTRs.The 3’UTR affects m RNA stability,translation,transportation,and cellular localization.Therefore,APA is an important mechanism of posttranscriptional gene regulation in eukaryotes.In recent years,whole genome sequencing of animals,plants and yeast has revealed that APA is pervasive in eukaryotes,and the functional consequences and regulation of APA have been studied.To date,many cis-acting regulatory elements and trans-acting factors for APA regulation have been identified.In this review,we summarize the recent advances in the functional consequences and regulation of APA and discuss the future directions,aiming to provide clues and references for future APA study.