ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2023, Vol. 32 ›› Issue (5): 466-471.DOI: 10.3969/j.issn.1006-298X.2023.05.014

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转录后选择性多聚腺苷酸化调控与糖尿病肾病

  

  • 出版日期:2023-10-28 发布日期:2023-10-25

Alternative polyadenylation and diabetic nephropathy

  • Online:2023-10-28 Published:2023-10-25

摘要: 选择性多聚腺苷酸化(alternative polyadenylation,APA)作为重要的转录后调控机制,是真核细胞mRNA成熟过程中,由于不同多聚腺苷酸化信号位点的选择导致一个基因产生多个3'UTR 序列长度不同的转录异构体,其中premRNA序列中的顺式调控元件、对应的反式作用因子,例如细胞核中多种酶和蛋白因子等共同参与APA调控。研究发现,APA机制参与多种生理、病理进程,主要通过改变3'UTR 序列长度影响对应反式作用因子的调控作用,进而调节mRNA定位、稳定性、翻译效率及蛋白的定位等。本文将系统阐述转录后APA的作用机制和研究现状,并结合新近研究进展,探讨APA在糖尿病肾病研究中的前景。


关键词: 选择性多聚腺苷酸化, 转录后调控, 糖尿病肾病 

Abstract: Alternative polyadenylation (APA), as a crucial post-transcriptional regulatory mechanism, has been reported to generate distinct transcripts with variable 3′UTR lengths by selecting different polyadenylation sites (polyA sites, PAS) in 3′UTR. The cis-regulatory elements in pre-mRNA, corresponding trans-acting factors, as well as various enzymes and protein factors in the nucleus are involved in the regulation of APA. Many cis-regulatory elements, such as microRNA (miRNA) or RNA-binding protein (RBP) binding sites, are embedded in the 3′UTR sequence, therefore, the presence or absence of these cis-acting elements conferred by 3′UTR-APA has far-reaching effects on the stability, translation rate, nuclear export, cellular localization of target mRNAs, as well as proteins localization. APA-associated genetic variants have been proposed to affect diverse physiological and pathological processes. Here, we will systematically elaborate the regulatory mechanism of APA and its research progress in diabetic nephropathy.

Key words: alternative polyadenylation, post-transcriptional regulation, diabetic nephropathy