功能与疾病中的RBFox蛋白家族

广东省基因组稳定性与疾病防治重点实验室,深圳大学医学部基础医学院,广东深圳518060

分子生物学; RNA结合蛋白; RBFox; RNA识别结构域; 多功能蛋白; 疾病调控

RBFox family proteins in function and disease regulation
WEI Chaoliang, XIA Ming, and GU Mingyao

Guangdong Key Laboratory of Genomic Stability and Disease Control, School of Basic Medicine Science, Health Science Center, Shenzhen University, Shenzhen 518060, Guangdong Province, P.R.China

molecular biology; RNA binding protein; RBFox; RNA recognition motif; multifunctional protein; disease regulation

DOI: 10.3724/SP.J.1249.2020.05514

备注

RNA结合蛋白(RNA binding proteins, RBPs)是细胞内一类能与单链或双链核糖核酸(ribonuleic acid, RNA)结合并形成核糖核蛋白复合体的一类蛋白.RBFox(RNA binding proteins feminine gene on X chromosome)蛋白是RNA结合蛋白家族中的重要成员,在多种动物体内的特定组织细胞中表达并发挥生物学功能.已发现的RBFox蛋白包括RBFox1、RBFox2和RBFox3,均含有进化上高度保守的RNA识别结构基序(RNA recognition motif, RRM),能特异性地与(U)GCAUG序列结合并发挥作用.目前研究揭示了RBFox蛋白是一类多功能蛋白,除了调控RNA加工过程中的经典功能可变剪接之外,还广泛参与基因转录、mRNA稳定性调节、miRNA代谢以及蛋白翻译等过程,在心脏疾病、神经系统疾病、糖尿病和癌症等疾病的发生发展过程中起重要调控作用.本文概述了目前RBFox家族在调节剪接、转录、miRNA代谢和mRNA稳定性的4个功能及其在心脏疾病、神经系统疾病、糖尿病和癌症等多种疾病方面的研究进展,为RBFox蛋白的作用机制及其对疾病调控的进一步研究提供借鉴.

RNA binding proteins(RBPs)are a class of intracellular proteins that bind to single-stranded or double-stranded RNA and form a ribonucleoprotein complex. RBFox(RNA binding proteins feminine gene on X chromosome)proteins are important members of the RNA-binding protein family and are expressed in specific tissue and cells of various animals, where they play important biological functions. Three members of the RBFox proteins, which are RBFox1, RBFox2 and RBFox3, have been discovered, and all of them contain an evolutionarily highly conserved RNA recognition motif(RRM), which specifically binds to the(U)GCAUG sequence. Current studies reveal that RBFox proteins are a kind of multifunctional proteins. In addition to regulating the classical functions of alternative splicing in RNA processing, they are also widely involved in transcription, mRNA stability, miRNA metabolism and translation processes. The RBFox proteins play pathological roles in the onset and development of many diseases including heart disease, neurological diseases, diabetes and cancer. This article gives the regulatory functions of RBFox family in splicing, transcription, miRNA metabolism and mRNA stability, and its related research progresses in heart disease, neurological disease, diabetes, cancer and other diseases. It provides a reference for further study on mechanism and disease regulation of RBFox proteins.

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