动物 microRNA 诱导的沉默复合物的调控和不同功能,WIREs RNA

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动物 microRNA 诱导的沉默复合物的调控和不同功能
WIREs RNA ( IF 6.4 ) Pub Date : 2021-11-01 , DOI: 10.1002/wrna.1701
Pierre‐Marc Frédérick _{1,

2} , Martin J. Simard _{1,

2}

Affiliation

在不同类型的小 RNA 中，microRNA (miRNA) 是在 mRNA 水平上控制基因表达的关键角色。为了发挥活性，它们必须与 Argonaute 蛋白结合以形成 miRNA 诱导的沉默复合物 (miRISC)，并通过互补序列与特定的 mRNA 结合。miRISC 与 mRNA 的结合可导致多种结果，最常见的是抑制翻译和/或去腺苷酸化，然后是脱帽和 mRNA 衰变。在过去几年中，几项研究描述了调节动物 miRISC 功能的不同机制。例如，通过翻译后修饰对 Argonaute 蛋白的调节可以改变 miRISC 基因的调节活性，并调节其与蛋白质、mRNA 靶标和 miRISC 稳定性的结合。此外，靶mRNA 3'非翻译区（3'UTR）处存在RNA结合蛋白和多个miRISC也可以通过合作或竞争机制影响其功能，这表明3'UTR环境在miRNA介导的抑制中的重要性。调节 miRISC 功能的另一种方法是通过调节其相互作用物，形成不同类型的 miRNA 沉默复合物，以不同方式影响基因调控。据报道，miRNA 通路的几种成分的亚细胞定位可以调节 miRISC 功能，这表明囊泡运输在调节这种必需的沉默复合物中起重要作用。3'UTR 环境在 miRNA 介导的抑制中的重要性。调节 miRISC 功能的另一种方法是通过调节其相互作用物，形成不同类型的 miRNA 沉默复合物，以不同方式影响基因调控。据报道，miRNA 通路的几种成分的亚细胞定位可以调节 miRISC 功能，这表明囊泡运输在调节这种必需的沉默复合物中起重要作用。3'UTR 环境在 miRNA 介导的抑制中的重要性。调节 miRISC 功能的另一种方法是通过调节其相互作用物，形成不同类型的 miRNA 沉默复合物，以不同方式影响基因调控。据报道，miRNA 通路的几种成分的亚细胞定位可以调节 miRISC 功能，这表明囊泡运输在调节这种必需的沉默复合物中起重要作用。

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Regulation and different functions of the animal microRNA-induced silencing complex

Among the different types of small RNAs, microRNAs (miRNAs) are key players in controlling gene expression at the mRNA level. To be active, they must associate with an Argonaute protein to form the miRNA induced silencing complex (miRISC) and binds to specific mRNA through complementarity sequences. The miRISC binding to an mRNA can lead to multiple outcomes, the most frequent being inhibition of the translation and/or deadenylation followed by decapping and mRNA decay. In the last years, several studies described different mechanisms modulating miRISC functions in animals. For instance, the regulation of the Argonaute protein through post-translational modifications can change the miRISC gene regulatory activity as well as modulate its binding to proteins, mRNA targets and miRISC stability. Furthermore, the presence of RNA binding proteins and multiple miRISCs at the targeted mRNA 3′ untranslated region (3′UTR) can also affect its function through cooperation or competition mechanisms, underlying the importance of the 3′UTR environment in miRNA-mediated repression. Another way to regulate the miRISC function is by modulation of its interactors, forming different types of miRNA silencing complexes that affect gene regulation differently. It is also reported that the subcellular localization of several components of the miRNA pathway can modulate miRISC function, suggesting an important role for vesicular trafficking in the regulation of this essential silencing complex.

更新日期：2021-11-01

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