靶向 microRNA 降解:机制、意义和功能影响。

IF 6.4 2区 生物学 Q1 CELL BIOLOGY
Nicholas M Hiers, Tianqi Li, Conner M Traugot, Mingyi Xie
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引用次数: 0

摘要

微小RNA(miRNA)是一种小型非编码RNA,在miRNA介导的目标抑制中发挥着基础性作用,这是一种转录后基因调控机制,在元古宙中得以保留。某些动物 miRNA 基因的缺失会导致发育异常、疾病和不同程度的胚胎死亡。这些短 RNA 通常会引导 Argonaute(AGO)蛋白找到靶 RNA,进而抑制靶 RNA 的翻译并使其不稳定,从而沉默靶 RNA,以微调基因表达并维持细胞稳态。数以千计的研究对 miRNA 介导的靶衰变进行了深入探讨,然而,尽管进行了这些详尽的研究,人们对 miRNA 如何以及为何被定向衰变的了解却相对较少。多年来的一些重要观察发现了 miRNA 快速更替的情况,这表明动物有诱导 miRNA 降解的内源性手段。最近,有研究发现,某些靶标,即所谓的靶标引导的 miRNA 降解(TDMD)触发器,可以通过诱导 AGO 蛋白分解从而 "触发 "miRNA 的降解。在动物体内,这一过程是通过 ZSWIM8 泛素连接酶复合物介导的。自 ZSWIM8 和 TDMD 被发现以来,已有多项研究发现它们对动物的正常发育不可或缺。鉴于这一研究领域的迅速扩展,我们在此总结了发现 ZSWIM8 依赖性 TDMD 之前和之后的主要发现。本文归类于调控 RNAs/RNAi/Riboswitches > 调控 RNAs RNA 更替与监控 > 更替/监控机制 RNA 在疾病与发育中的作用 > RNA 在发育中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Target-directed microRNA degradation: Mechanisms, significance, and functional implications.

MicroRNAs (miRNAs) are small non-coding RNAs that play a fundamental role in enabling miRNA-mediated target repression, a post-transcriptional gene regulatory mechanism preserved across metazoans. Loss of certain animal miRNA genes can lead to developmental abnormalities, disease, and various degrees of embryonic lethality. These short RNAs normally guide Argonaute (AGO) proteins to target RNAs, which are in turn translationally repressed and destabilized, silencing the target to fine-tune gene expression and maintain cellular homeostasis. Delineating miRNA-mediated target decay has been thoroughly examined in thousands of studies, yet despite these exhaustive studies, comparatively less is known about how and why miRNAs are directed for decay. Several key observations over the years have noted instances of rapid miRNA turnover, suggesting endogenous means for animals to induce miRNA degradation. Recently, it was revealed that certain targets, so-called target-directed miRNA degradation (TDMD) triggers, can "trigger" miRNA decay through inducing proteolysis of AGO and thereby the bound miRNA. This process is mediated in animals via the ZSWIM8 ubiquitin ligase complex, which is recruited to AGO during engagement with triggers. Since its discovery, several studies have identified that ZSWIM8 and TDMD are indispensable for proper animal development. Given the rapid expansion of this field of study, here, we summarize the key findings that have led to and followed the discovery of ZSWIM8-dependent TDMD. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA in Disease and Development > RNA in Development.

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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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