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天然和合成 RNA 结合蛋白在癌症中对 miRNA 功能的调控。

Modulation of miRNA function by natural and synthetic RNA-binding proteins in cancer.

机构信息

Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, 6009, Australia.

Centre for Medical Research, The University of Western Australia, Nedlands, WA, 6009, Australia.

出版信息

Cell Mol Life Sci. 2019 Oct;76(19):3745-3752. doi: 10.1007/s00018-019-03163-9. Epub 2019 Jun 4.

Abstract

RNA-binding proteins (RBPs) and microRNAs (miRNAs) are the most important regulators of mRNA stability and translation in eukaryotic cells; however, the complex interplay between these systems is only now coming to light. RBPs and miRNAs regulate a unique set of targets in either a positive or negative manner and their regulation is mainly opposed to each other on overlapping targets. In some cases, the levels of RBPs or miRNAs regulate the cellular levels of one another and decreased levels of either results in changes in translation of their targets. There is growing evidence that these regulatory circuits are crucial in the development and progression of cancer; however, the rules underlying synergism and antagonism between miRNAs and RNA-binding proteins remain unclear. Synthetic biology seeks to develop artificial systems to better understand their natural counterparts and to develop new, useful technologies for manipulation of gene expression at the RNA level. The recent development of artificial RNA-binding proteins promises to enable a much greater understanding of the importance of the functional interactions between RNA-binding proteins and miRNAs, as well as enabling their manipulation for therapeutic purposes.

摘要

RNA 结合蛋白 (RBPs) 和 microRNAs (miRNAs) 是真核细胞中 mRNA 稳定性和翻译的最重要调节剂;然而,这些系统之间的复杂相互作用现在才开始显现出来。RBPs 和 miRNAs 以正向或负向方式调节一组独特的靶标,它们的调节主要在重叠靶标上相互拮抗。在某些情况下,RBPs 或 miRNAs 的水平调节彼此的细胞水平,而两者水平的降低都会导致其靶标的翻译发生变化。越来越多的证据表明,这些调控回路在癌症的发生和发展中至关重要;然而,miRNAs 和 RNA 结合蛋白之间协同作用和拮抗作用的规则仍不清楚。合成生物学旨在开发人工系统,以更好地了解它们的天然对应物,并开发新的、有用的技术,用于在 RNA 水平上操纵基因表达。最近人工 RNA 结合蛋白的发展有望使我们更深入地了解 RNA 结合蛋白和 miRNAs 之间功能相互作用的重要性,并能够为治疗目的对其进行操纵。

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