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首页> 外文期刊>The FEBS journal >TDP-43: new aspects of autoregulation mechanisms in RNA binding proteins and their connection with human disease
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TDP-43: new aspects of autoregulation mechanisms in RNA binding proteins and their connection with human disease

机译：TDP-43：RNA结合蛋白中自动调节机制及其与人类疾病的关系的新方面

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摘要

The maintenance of correct protein homeostasis ('proteostasis') is an essential activity of mammalian cells to preserve their vital properties and functions. Because of its importance, correct proteostasis is achieved by the cell in several ways and at several levels of each gene expression pathway. In many cases, mRNA-autoregulatory pathways based on a variety of feedback mechanisms have been observed to play a major role in keeping their concentration under control. This is especially true for RNA binding proteins because of their potential ability to bind their own pre-mRNA molecules, and in particular for two subsets of nuclear factors that are commonly referred to as heterogeneous ribonucleoproteins and serine-arginine-rich proteins. Regarding the mechanism, nonsense-mediated RNA degradation triggered by alternative splicing of their own messenger RNA is a very common autoregulation pathway to maintain constant expression levels within the cellular environment. Recently, however, alternative mechanisms other than nonsense-mediated decay have also been described to play a role for other RNA binding protein factors: serine-arginine-rich splicing factor 1 (SRSF1) and transactive response DNA binding protein 43 kDa (TDP-43). The aim of this minireview will be to discuss these old and new autoregulatory processes and their implication in disease development.
机译：维持正确的蛋白质稳态（“蛋白质稳态”）是哺乳动物细胞维持其重要特性和功能的一项基本活动。由于其重要性，细胞可以通过几种方式在每种基因表达途径的几种水平上实现正确的蛋白稳态。在许多情况下，已观察到基于多种反馈机制的mRNA自我调节途径在控制其浓度方面起着重要作用。对于RNA结合蛋白尤其如此，因为它们具有结合自身mRNA前体分子的潜在能力，特别是对于两个通常称为异质核糖核蛋白和富含丝氨酸精氨酸的核因子的子集。关于该机制，由其自身信使RNA的可变剪接引发的无意义介导的RNA降解是维持细胞环境内恒定表达水平的非常常见的自动调节途径。然而，最近，还描述了无意义介导的衰变以外的其他机制对其他RNA结合蛋白因子也起作用：富含丝氨酸精氨酸的剪接因子1（SRSF1）和交易应答DNA结合蛋白43 kDa（TDP-43 ）。这次迷你审查的目的是讨论这些新旧的自动调节过程及其对疾病发展的影响。

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