工程化 RNA 结合蛋白:研究和控制 RNA 调节

IF 2.3 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Riley W. Sinnott, Yang Cao, Bryan C. Dickinson
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引用次数: 0

摘要

1 引言RNA是真核生物遗传信息流动的关键中间体,其调控是动态基因表达和细胞特性的基础。1 RNA在细胞内如何通过改变其稳定性、化学成分、序列和翻译速率来进行调控一直是一个深入的研究领域,近几十年来的研究结果极大地提升了我们对RNA调控在中心教条中重要性的认识。2 具体来说,改变 RNA 组成的事件,如替代剪接和 3' 端加工,通过影响蛋白质的组成和定位,对真核生物的复杂性起着奠基性的作用。我们还逐渐认识到,RNA 结合蛋白(RBPs)和非编码 RNA(如 miRNA 或 lncRNA)对 mRNA 稳定性和翻译的调控可以独特地调节不同组织的蛋白质组平衡。最近,何川研究小组及其同事对 N6-甲基腺苷(m6A)修饰等 RNA 调控途径的研究为 "表转录组学 "领域的出现奠定了基础(图 1a)。图 1在图形浏览器中打开PowerPoint 表转录组学的突破使工程化平台能够指导和研究 RNA 调控。a, m6A 修饰由 "写入 "酶安装,并由 "擦除 "酶去除,"读取 "蛋白介导修饰 RNA 的下游调控。b.可编程 RBPs 可将融合的 "写入器 "或 "擦除器 "酶引向明确的 RNA 靶点,并影响其特定位点的修饰。RBPs 能识别并结合特定的 RNA 修饰或序列基团,从而对结合的 RNA 产生影响,它们是在 RNA 水平上驱动化学修饰依赖性基因表达变化的功能性主力军。事实上,我们开始认识到,同一种修饰可对特定 RNA 产生不同的下游效应,这取决于与之结合的 RBP(每种 RBP 都具有不同的特定活性和/或相互作用伙伴)7。RNA 调控所具有的强大功能和多变性激发了人们对 RBPs 能否被精确设计以可编程方式影响基因表达的浓厚兴趣(图 1b)。我们对 RNA 调控的理解不断进步,而可编程 DNA 靶向技术的最新突破又为工程方法提供了新的信息,在这两者的共同推动下,这一兴趣已凝聚成一个迅速扩展的领域。在这篇综述中,我们将讨论工程蛋白质结合特定 RNA 序列的最新进展,以及这些蛋白质的功能化,以指导改变 RNA 组成和/或命运的各种过程。我们还将重点介绍这些系统在基础研究中用于探测和研究生物系统的几种令人兴奋的应用,以及具有治疗功能的合成 RBPs,用于纠正错误的基因表达。最后,我们将介绍在利用 RBPs 之外的 RNA 调节方面取得的进一步进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Engineered RNA-Binding Proteins: Studying and Controlling RNA Regulation

Engineered RNA-Binding Proteins: Studying and Controlling RNA Regulation

Engineered RNA-Binding Proteins: Studying and Controlling RNA Regulation

The complexity of eukaryotic organisms is intricately tied to transcriptome-level processes, notably alternative splicing and the precise modulation of gene expression through a sophisticated interplay involving RNA-binding protein (RBP) networks and their RNA targets. Recent advances in our understanding of the molecular pathways responsible for this control have paved the way for the development of tools capable of steering and managing RNA regulation and gene expression. The fusion between a rapidly developing understanding of endogenous RNA regulation and the burgeoning capabilities of CRISPR-Cas and other programmable RBP platforms has given rise to an exciting frontier in engineered RNA regulators. This review offers an overview of the existing toolkit for constructing synthetic RNA regulators using programmable RBPs and effector domains, capable of altering RNA sequence composition or fate, and explores their diverse applications in both basic research and therapeutic contexts.

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来源期刊
Israel Journal of Chemistry
Israel Journal of Chemistry 化学-化学综合
CiteScore
6.20
自引率
0.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: The fledgling State of Israel began to publish its scientific activity in 1951 under the general heading of Bulletin of the Research Council of Israel, which quickly split into sections to accommodate various fields in the growing academic community. In 1963, the Bulletin ceased publication and independent journals were born, with Section A becoming the new Israel Journal of Chemistry. The Israel Journal of Chemistry is the official journal of the Israel Chemical Society. Effective from Volume 50 (2010) it is published by Wiley-VCH. The Israel Journal of Chemistry is an international and peer-reviewed publication forum for Special Issues on timely research topics in all fields of chemistry: from biochemistry through organic and inorganic chemistry to polymer, physical and theoretical chemistry, including all interdisciplinary topics. Each topical issue is edited by one or several Guest Editors and primarily contains invited Review articles. Communications and Full Papers may be published occasionally, if they fit with the quality standards of the journal. The publication language is English and the journal is published twelve times a year.
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