定义 GW182 在维持 miRNA 稳定性方面的新作用。
Defining a new role of GW182 in maintaining miRNA stability.
机构信息
Department of Oral Biology, University of Florida, Gainesville, Florida 32610-0424, USA.
出版信息
EMBO Rep. 2012 Dec;13(12):1102-8. doi: 10.1038/embor.2012.160. Epub 2012 Oct 23.
Abstract
GW182 binds to Argonaute (AGO) proteins and has a central role in miRNA-mediated gene silencing. Using lentiviral shRNA-induced GW182 knockdown in HEK293 cells, this study identifies a new role of GW182 in regulating miRNA stability. Stably knocking down GW182 or its paralogue TNRC6B reduces transfected miRNA-mimic half-lives. Replenishment of GW182 family proteins, as well as one of its domain Δ12, significantly restores the stability of transfected miRNA-mimic. GW182 knockdown reduces miRNA secretion via secretory exosomes. Targeted siRNA screening identifies a 3'-5' exoribonuclease complex responsible for the miRNA degradation only when GW182 is knocked down. Immunoprecipitation further confirms that the presence of GW182 in the RISC complex is critical in protecting Argonaute-bound miRNA.
摘要
GW182 与 Argonaute（AGO）蛋白结合，并在 miRNA 介导的基因沉默中起核心作用。本研究通过慢病毒 shRNA 诱导 HEK293 细胞中的 GW182 敲低，鉴定出 GW182 在调节 miRNA 稳定性方面的新作用。稳定敲低 GW182 或其同源物 TNRC6B 会降低转染的 miRNA 模拟物的半衰期。GW182 家族蛋白的补充，以及其一个结构域 Δ12，可显著恢复转染的 miRNA 模拟物的稳定性。GW182 敲低通过分泌性外泌体减少 miRNA 的分泌。靶向 siRNA 筛选发现，只有在敲低 GW182 时，3'-5' 外切核酸酶复合物才负责 miRNA 的降解。免疫沉淀进一步证实，RISC 复合物中 GW182 的存在对于保护 Argonaute 结合的 miRNA 至关重要。
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1
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Nat Struct Mol Biol. 2011 Oct 7;18(11):1211-7. doi: 10.1038/nsmb.2149.
2
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。
Nat Struct Mol Biol. 2011 Oct 7;18(11):1218-26. doi: 10.1038/nsmb.2166.
3
GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets.GW182 蛋白直接将细胞质脱腺苷酶复合物招募到 miRNA 靶标上。
Mol Cell. 2011 Oct 7;44(1):120-33. doi: 10.1016/j.molcel.2011.09.007.
4
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RNA Biol. 2011 Nov-Dec;8(6):1149-57. doi: 10.4161/rna.8.6.17665. Epub 2011 Nov 1.
5
MicroRNA destabilization enables dynamic regulation of the miR-16 family in response to cell-cycle changes.MicroRNA 失稳使得 miR-16 家族能够响应细胞周期变化进行动态调节。
Mol Cell. 2011 Sep 16;43(6):993-1004. doi: 10.1016/j.molcel.2011.08.021.
6
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7
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8
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9
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10
Differential regulation of microRNA stability.微小 RNA 稳定性的差异调控。
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