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miRISCs 和去腺苷酶之间的分子联系为 microRNAs 基因沉默机制提供了新的见解。

A molecular link between miRISCs and deadenylases provides new insight into the mechanism of gene silencing by microRNAs.

机构信息

Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany.

出版信息

Cold Spring Harb Perspect Biol. 2012 Dec 1;4(12):a012328. doi: 10.1101/cshperspect.a012328.

DOI:10.1101/cshperspect.a012328
PMID:23209154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3504443/
Abstract

MicroRNAs (miRNAs) are a large family of endogenous noncoding RNAs that, together with the Argonaute family of proteins (AGOs), silence the expression of complementary mRNA targets posttranscriptionally. Perfectly complementary targets are cleaved within the base-paired region by catalytically active AGOs. In the case of partially complementary targets, however, AGOs are insufficient for silencing and need to recruit a protein of the GW182 family. GW182 proteins induce translational repression, mRNA deadenylation and exonucleolytic target degradation. Recent work has revealed a direct molecular link between GW182 proteins and cellular deadenylase complexes. These findings shed light on how miRNAs bring about target mRNA degradation and promise to further our understanding of the mechanism of miRNA-mediated repression.

摘要

微小 RNA（miRNAs）是一大类内源性非编码 RNA，它们与 Argonaute 家族蛋白（AGOs）一起，在后转录水平上沉默互补 mRNA 靶标的表达。完全互补的靶标在碱基配对区域被具有催化活性的 AGO 切割。然而，对于部分互补的靶标，AGO 不足以沉默，需要招募 GW182 家族的蛋白质。GW182 蛋白诱导翻译抑制、mRNA 去腺苷酸化和外切核酸酶靶标降解。最近的工作揭示了 GW182 蛋白和细胞脱腺苷酸酶复合物之间的直接分子联系。这些发现揭示了 miRNA 如何导致靶 mRNA 降解，并有望进一步加深我们对 miRNA 介导的抑制机制的理解。

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本文引用的文献

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miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay.miRNA 介导的基因沉默通过翻译抑制 followed by mRNA 去腺苷酸化和降解。
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The Caenorhabditis elegans GW182 protein AIN-1 interacts with PAB-1 and subunits of the PAN2-PAN3 and CCR4-NOT deadenylase complexes.秀丽隐杆线虫的 GW182 蛋白 AIN-1 与 PAB-1 以及 PAN2-PAN3 和 CCR4-NOT 去腺苷酸酶复合物的亚基相互作用。
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A team effort blocks the ribosome in its tracks.团队合作使核糖体停滞不前。
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Translational inhibition by deadenylation-independent mechanisms is central to microRNA-mediated silencing in zebrafish.去腺苷酸化非依赖性机制的翻译抑制是斑马鱼中 microRNA 介导的沉默的核心。
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Mutations in the GW-repeat protein SUO reveal a developmental function for microRNA-mediated translational repression in Arabidopsis.GW 重复蛋白 SUO 的突变揭示了 miRNA 介导的翻译抑制在拟南芥发育中的作用。
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PABP is not essential for microRNA-mediated translational repression and deadenylation in vitro.PABP 对于体外 microRNA 介导的翻译抑制和去腺苷酸化并非必需。
EMBO J. 2011 Nov 25;30(24):4998-5009. doi: 10.1038/emboj.2011.426.
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Non-coding RNAs in human disease.人类疾病中的非编码 RNA。
Nat Rev Genet. 2011 Nov 18;12(12):861-74. doi: 10.1038/nrg3074.
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miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT.miRNA 介导的去腺苷酸化是由 GW182 通过与 CCR4-NOT 相互作用的两个保守基序来协调的。
Nat Struct Mol Biol. 2011 Oct 7;18(11):1211-7. doi: 10.1038/nsmb.2149.
10
miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs.miRNA 抑制涉及通过保守的 W 结构域结合基序介导的 GW182 募集 CCR4-NOT。
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