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可变RNA剪接在脂肪生成和人类代谢健康中的调控作用及机制

Regulatory roles and mechanisms of alternative RNA splicing in adipogenesis and human metabolic health.

作者信息

Chao Yunqi, Jiang Yonghui, Zhong Mianling, Wei Kaiyan, Hu Chenxi, Qin Yifang, Zuo Yiming, Yang Lili, Shen Zheng, Zou Chaochun

机构信息

Department of Endocrinology, The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310052, Zhejiang, China.

Department of Genetics, Yale University School of Medicine, New Haven, CT, 06520, USA.

出版信息

Cell Biosci. 2021 Apr 1;11(1):66. doi: 10.1186/s13578-021-00581-w.

Abstract

Alternative splicing (AS) regulates gene expression patterns at the post-transcriptional level and generates a striking expansion of coding capacities of genomes and cellular protein diversity. RNA splicing could undergo modulation and close interaction with genetic and epigenetic machinery. Notably, during the adipogenesis processes of white, brown and beige adipocytes, AS tightly interplays with the differentiation gene program networks. Here, we integrate the available findings on specific splicing events and distinct functions of different splicing regulators as examples to highlight the directive biological contribution of AS mechanism in adipogenesis and adipocyte biology. Furthermore, accumulating evidence has suggested that mutations and/or altered expression in splicing regulators and aberrant splicing alterations in the obesity-associated genes are often linked to humans' diet-induced obesity and metabolic dysregulation phenotypes. Therefore, significant attempts have been finally made to overview novel detailed discussion on the prospects of splicing machinery with obesity and metabolic disorders to supply featured potential management mechanisms in clinical applicability for obesity treatment strategies.

摘要

可变剪接(AS)在转录后水平调控基因表达模式,并显著扩展了基因组的编码能力和细胞蛋白质多样性。RNA剪接可受到调控,并与遗传和表观遗传机制密切相互作用。值得注意的是,在白色、棕色和米色脂肪细胞的脂肪生成过程中,可变剪接与分化基因程序网络紧密相互作用。在此,我们整合了关于特定剪接事件和不同剪接调节因子独特功能的现有研究结果,以突出可变剪接机制在脂肪生成和脂肪细胞生物学中的直接生物学贡献。此外,越来越多的证据表明,剪接调节因子的突变和/或表达改变以及肥胖相关基因的异常剪接改变通常与人类饮食诱导的肥胖和代谢失调表型有关。因此,最终人们进行了大量尝试,全面概述关于剪接机制与肥胖和代谢紊乱关系的新颖详细讨论,以提供肥胖治疗策略临床应用中具有特色的潜在管理机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ae/8017860/a85287656657/13578_2021_581_Fig1_HTML.jpg

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