Undervalued and novel roles of heterogeneous nuclear ribonucleoproteins in autoimmune diseases: Resurgence as potential biomarkers and targets.

IF 6.4 2区 生物学 Q1 CELL BIOLOGY Wiley Interdisciplinary Reviews: RNA Pub Date : 2023-11-01 Epub Date: 2023-06-26 DOI:10.1002/wrna.1806
Kangzhi Chen, Mengchuan Luo, Yuanzhi Lv, Zhaohui Luo, Huan Yang
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Abstract

Autoimmune diseases are mainly characterized by the abnormal autoreactivity due to the loss of tolerance to specific autoantigens, though multiple pathways associated with the homeostasis of immune responses are involved in initiating or aggravating the conditions. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a major category of RNA-binding proteins ubiquitously expressed in a multitude of cells and have attracted great attentions especially with their distinctive roles in nucleic acid metabolisms and the pathogenesis in diseases like neurodegenerative disorders and cancers. Nevertheless, the interplay between hnRNPs and autoimmune disorders has not been fully elucidated. Virtually various family members of hnRNPs are increasingly identified as immune players and are pertinent to all kinds of immune-related processes including immune system development and innate or adaptive immune responses. Specifically, hnRNPs have been extensively recognized as autoantigens within and even beyond a myriad of autoimmune diseases, yet their diagnostic and prognostic values are seemingly underestimated. Molecular mimicry, epitope spreading and bystander activation may represent major putative mechanisms underlying the presence of autoantibodies to hnRNPs. Besides, hnRNPs play critical parts in regulating linchpin genes expressions that control genetic susceptibility, disease-linked functional pathways, or immune responses by interacting with other components particularly like microRNAs and long non-coding RNAs, thereby contributing to inflammation and autoimmunity as well as specific disease phenotypes. Therefore, comprehensive unraveling of the roles of hnRNPs is conducive to establishing potential biomarkers and developing better intervention strategies by targeting these hnRNPs in the corresponding disorders. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

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异质核核糖核蛋白在自身免疫性疾病中被低估的新作用:作为潜在生物标志物和靶标的复兴
自身免疫性疾病的主要特征是由于对特定自身抗原的耐受性丧失而导致的自身反应性异常,尽管与免疫反应稳态相关的多种途径参与了疾病的启动或加重。异质核核糖核蛋白(hnRNPs)是一类广泛存在于多种细胞中的rna结合蛋白,因其在神经退行性疾病和癌症等疾病的核酸代谢和发病机制中具有独特的作用而备受关注。然而,hnRNPs与自身免疫性疾病之间的相互作用尚未完全阐明。事实上,hnRNPs的各种家族成员越来越多地被确定为免疫参与者,并与各种免疫相关的过程有关,包括免疫系统发育和先天或适应性免疫反应。具体来说,hnRNPs已被广泛认为是自身抗原,甚至超越了无数自身免疫性疾病,但它们的诊断和预后价值似乎被低估了。分子模仿、表位扩散和旁观者激活可能是hnRNPs自身抗体存在的主要推测机制。此外,hnRNPs通过与其他组分(特别是microRNAs和长链非编码rna)相互作用,在调节控制遗传易感性、疾病相关功能通路或免疫反应的关键基因表达方面发挥关键作用,从而促进炎症和自身免疫以及特定疾病表型。因此,全面揭示hnRNPs的作用有助于建立潜在的生物标志物,并通过针对这些hnRNPs在相应疾病中制定更好的干预策略。本文分类为:RNA在疾病和发展中的作用> RNA在疾病中的作用RNA与蛋白质和其他分子的相互作用>蛋白质-RNA相互作用:功能意义。
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来源期刊
CiteScore
14.80
自引率
4.10%
发文量
67
审稿时长
6-12 weeks
期刊介绍: WIREs RNA aims to provide comprehensive, up-to-date, and coherent coverage of this interesting and growing field, providing a framework for both RNA experts and interdisciplinary researchers to not only gain perspective in areas of RNA biology, but to generate new insights and applications as well. Major topics to be covered are: RNA Structure and Dynamics; RNA Evolution and Genomics; RNA-Based Catalysis; RNA Interactions with Proteins and Other Molecules; Translation; RNA Processing; RNA Export/Localization; RNA Turnover and Surveillance; Regulatory RNAs/RNAi/Riboswitches; RNA in Disease and Development; and RNA Methods.
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