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自身免疫中的转录后检查点。

Post-transcriptional checkpoints in autoimmunity.

机构信息

Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184), Le Kremlin Bicêtre, France.

Institut Curie, CNRS UMR3348, INSERM U1278, PSL Research University, Université Paris-Saclay, Orsay, France.

出版信息

Nat Rev Rheumatol. 2023 Aug;19(8):486-502. doi: 10.1038/s41584-023-00980-y. Epub 2023 Jun 13.

Abstract

Post-transcriptional regulation is a fundamental process in gene expression that has a role in diverse cellular processes, including immune responses. A core concept underlying post-transcriptional regulation is that protein abundance is not solely determined by transcript abundance. Indeed, transcription and translation are not directly coupled, and intervening steps occur between these processes, including the regulation of mRNA stability, localization and alternative splicing, which can impact protein abundance. These steps are controlled by various post-transcription factors such as RNA-binding proteins and non-coding RNAs, including microRNAs, and aberrant post-transcriptional regulation has been implicated in various pathological conditions. Indeed, studies on the pathogenesis of autoimmune and inflammatory diseases have identified various post-transcription factors as important regulators of immune cell-mediated and target effector cell-mediated pathological conditions. This Review summarizes current knowledge regarding the roles of post-transcriptional checkpoints in autoimmunity, as evidenced by studies in both haematopoietic and non-haematopoietic cells, and discusses the relevance of these findings for developing new anti-inflammatory therapies.

摘要

转录后调控是基因表达的一个基本过程,在包括免疫反应在内的多种细胞过程中都有作用。转录后调控的一个核心概念是,蛋白质丰度不仅仅由转录物丰度决定。实际上,转录和翻译并没有直接偶联,在这些过程之间会发生中间步骤,包括 mRNA 稳定性、定位和选择性剪接的调节,这些都可以影响蛋白质丰度。这些步骤由各种转录后因子控制,如 RNA 结合蛋白和非编码 RNA,包括 microRNAs,异常的转录后调控与各种病理状况有关。事实上,对自身免疫和炎症性疾病发病机制的研究已经确定了各种转录后因子作为免疫细胞介导和靶效应细胞介导的病理状况的重要调节剂。这篇综述总结了目前关于转录后检查点在自身免疫中的作用的知识,这些知识来自于造血和非造血细胞的研究,并讨论了这些发现对于开发新的抗炎治疗方法的相关性。

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