选择性拼接
RNA结合蛋白
RNA剪接
三素数非翻译区
基因亚型
信使核糖核酸
非翻译区
生物
外显子
小RNA
细胞生物学
核糖核酸
强直性营养不良
翻译(生物学)
基因表达
遗传学
基因
作者
Arkadiusz Kajdasz,Daria Niewiadomska,Michał Sekrecki,Krzysztof Sobczak
标识
DOI:10.1038/s41598-021-03901-9
摘要
Abstract CUG-binding protein, ELAV-like Family Member 1 (CELF1) plays an important role during the development of different tissues, such as striated muscle and brain tissue. CELF1 is an RNA-binding protein that regulates RNA metabolism processes, e.g., alternative splicing, and antagonizes other RNA-binding proteins, such as Muscleblind -like proteins (MBNLs). Abnormal activity of both classes of proteins plays a crucial role in the pathogenesis of myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults. In this work, we show that alternative splicing of exons forming both the 5′ and 3′ untranslated regions (UTRs) of CELF1 mRNA is efficiently regulated during development and tissue differentiation and is disrupted in skeletal muscles in the context of DM1. Alternative splicing of the CELF1 5′UTR leads to translation of two potential protein isoforms that differ in the lengths of their N-terminal domains. We also show that the MBNL and CELF proteins regulate the distribution of mRNA splicing isoforms with different 5′UTRs and 3′UTRs and affect the CELF1 expression by changing its sensitivity to specific microRNAs or RNA-binding proteins. Together, our findings show the existence of different mechanisms of regulation of CELF1 expression through the distribution of various 5′ and 3′ UTR isoforms within CELF1 mRNA.
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