Target‐directed microRNA degradation: Mechanisms, significance, and functional implications,Wiley Interdisciplinary Reviews: RNA

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Target‐directed microRNA degradation: Mechanisms, significance, and functional implications
Wiley Interdisciplinary Reviews: RNA Pub Date : 2024-03-06 , DOI: 10.1002/wrna.1832
Nicholas M Hiers ₁ , Tianqi Li ₁ , Conner M Traugot ₁ , Mingyi Xie ₁

Affiliation

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

中文翻译：

靶向 microRNA 降解：机制、意义和功能意义

MicroRNA (miRNA) 是一种小型非编码 RNA，在 miRNA 介导的靶标抑制（一种在后生动物中保留的转录后基因调控机制）中发挥着重要作用。某些动物 miRNA 基因的丢失可能导致发育异常、疾病和不同程度的胚胎致死。这些短 RNA 通常引导 Argonaute (AGO) 蛋白靶向 RNA，而 RNA 反过来又受到翻译抑制和不稳定，使靶标沉默，从而微调基因表达并维持细胞稳态。数千项研究已经对 miRNA 介导的靶标衰减进行了彻底的研究，但尽管有这些详尽的研究，但人们对 miRNA 如何以及为何定向衰减的了解相对较少。多年来的几个关键观察结果已经注意到 miRNA 快速更新的情况，表明动物存在诱导 miRNA 降解的内源性手段。最近，研究发现某些目标，即所谓的目标定向 miRNA 降解 (TDMD) 触发器，可以通过诱导 AGO 的蛋白水解以及结合的 miRNA 来“触发”miRNA 降解。在动物中，这一过程是通过 ZSWIM8 泛素连接酶复合物介导的，该复合物在与触发器接触期间被招募到 AGO。自发现以来，多项研究已确定 ZSWIM8 和 TDMD 对于动物的正常发育是不可或缺的。鉴于这一研究领域的迅速扩展，我们在此总结了导致 ZSWIM8 依赖性 TDMD 发现和发现的关键发现。本文分类如下：调节 RNA/RNAi/核糖开关 > 调节 RNA RNA 周转和监测 > 周转/监测机制疾病和发育中的 RNA > 发育中的 RNA

更新日期：2024-03-06

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