The new (dis)order in RNA regulation.

The new (dis)order in RNA regulation.
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DOI:
10.1186/s12964-016-0132-3
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发表时间:
2016-04-06
期刊:
Cell communication and signaling : CCS
影响因子:
--
通讯作者:
Castello A
Castello A
中科院分区:
其他
文献类型:
--
作者:
Järvelin AI;Noerenberg M;Davis I;Castello A

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RNA结合蛋白在RNA代谢的各个方面(从RNA的合成到其衰变)的调节中起着关键作用。蛋白质-RNA相互作用被认为主要由形成稳定的二级和三级结构的典型RNA结合结构域介导。然而,在过去的几十年里,一些开创性的研究,以及最近的蛋白质组数据,已经挑战了这一观点,揭示了内在无序的蛋白质区域在RNA结合中的惊人作用。在这里,我们讨论了无序的蛋白质区域如何介导蛋白质-RNA相互作用,在概念上将这些区域分为RS丰富,RG丰富和其他基本序列,可以介导与RNA的特异性和非特异性相互作用。无序区域也可以通过蛋白质聚集和水凝胶形成影响RNA代谢。重要的是,由无序区域介导的蛋白质-RNA相互作用几乎可以影响共转录和转录后RNA过程的所有方面,因此,它们的破坏可能导致疾病。尽管人们对无序蛋白质区域及其在RNA生物学中的作用越来越感兴趣,但对其结合,调节和生理后果的机制仍然知之甚少。在未来的几年里,这些非正统的相互作用的研究将产生重要的见解RNA调节细胞内稳态和疾病。本文的在线版本(doi:10.1186/s12964-016-0132-3)包含补充材料,可供授权用户使用。
RNA-binding proteins play a key role in the regulation of all aspects of RNA metabolism, from the synthesis of RNA to its decay. Protein-RNA interactions have been thought to be mostly mediated by canonical RNA-binding domains that form stable secondary and tertiary structures. However, a number of pioneering studies over the past decades, together with recent proteome-wide data, have challenged this view, revealing surprising roles for intrinsically disordered protein regions in RNA binding. Here, we discuss how disordered protein regions can mediate protein-RNA interactions, conceptually grouping these regions into RS-rich, RG-rich, and other basic sequences, that can mediate both specific and non-specific interactions with RNA. Disordered regions can also influence RNA metabolism through protein aggregation and hydrogel formation. Importantly, protein-RNA interactions mediated by disordered regions can influence nearly all aspects of co- and post-transcriptional RNA processes and, consequently, their disruption can cause disease. Despite growing interest in disordered protein regions and their roles in RNA biology, their mechanisms of binding, regulation, and physiological consequences remain poorly understood. In the coming years, the study of these unorthodox interactions will yield important insights into RNA regulation in cellular homeostasis and disease. The online version of this article (doi:10.1186/s12964-016-0132-3) contains supplementary material, which is available to authorized users.