关键词: RNA processing alternative polyadenylation cleavage and polyadenylation co-transcriptional alternative polyadenylation mRNA 3′ end formation sequential alternative polyadenylation

Mesh : Polyadenylation Transcription, Genetic Protein Isoforms / genetics RNA, Messenger / genetics metabolism 3' Untranslated Regions / genetics

来  源:   DOI:10.14348/molcells.2023.2176   PDF(Pubmed)

Abstract:
In eukaryotic cells, a key RNA processing step to generate mature mRNA is the coupled reaction for cleavage and polyadenylation (CPA) at the 3\' end of individual transcripts. Many transcripts are alternatively polyadenylated (APA) to produce mRNAs with different 3\' ends that may either alter protein coding sequence (CDS-APA) or create different lengths of 3\'UTR (tandem-APA). As the CPA reaction is intimately associated with transcriptional termination, it has been widely assumed that APA is regulated cotranscriptionally. Isoforms terminated at different regions may have distinct RNA stability under different conditions, thus altering the ratio of APA isoforms. Such differential impacts on different isoforms have been considered as post-transcriptional APA, but strictly speaking, this can only be considered \"apparent\" APA, as the choice is not made during the CPA reaction. Interestingly, a recent study reveals sequential APA as a new mechanism for post-transcriptional APA. This minireview will focus on this new mechanism to provide insights into various documented regulatory paradigms.
摘要:
在真核细胞中,产生成熟mRNA的关键RNA加工步骤是在单个转录物的3'末端进行切割和聚腺苷酸化(CPA)的偶联反应。许多转录物被选择性地聚腺苷酸化(APA)以产生具有不同3'末端的mRNA,这些mRNA可以改变蛋白质编码序列(CDS-APA)或产生不同长度的3'UTR(串联APA)。由于CPA反应与转录终止密切相关,人们普遍认为APA是共同转录调控的。不同区域终止的同种型在不同条件下可能具有不同的RNA稳定性。从而改变APA同工型的比例。对不同同工型的这种差异影响被认为是转录后APA,但严格来说,这只能被认为是“明显的”APA,因为在注册会计师反应期间没有做出选择。有趣的是,最近的一项研究揭示了序贯APA作为转录后APA的新机制。此小型审查将重点介绍这种新机制,以提供对各种记录在案的监管范式的见解。
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