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miRISC 成分 AGO2 有多个与 Nup358 SUMO 相互作用基序结合的位点。

The miRISC component AGO2 has multiple binding sites for Nup358 SUMO-interacting motif.

机构信息

National Centre for Cell Science, S.P. Pune University Campus, Pune, India.

Division of Biology, Indian Institute of Science Education and Research, Pune, India.

出版信息

Biochem Biophys Res Commun. 2021 Jun 4;556:45-52. doi: 10.1016/j.bbrc.2021.03.140. Epub 2021 Apr 7.

Abstract

Micro-RNA mediated suppression of mRNA translation represents a major regulatory mode of post-transcriptional gene expression. Recently, the nucleoporin Nup358 was shown to interact with AGO protein, a key component of miRNA-induced silencing complex (miRISC), and facilitate the coupling of miRISC with target mRNA. Previous results suggested that SUMO-interacting motifs (SIMs) present on Nup358 mediate interaction with AGO protein. Here we show that Nup358-SIM has multiple interacting regions on AGO2, specifically within the N, PAZ and MID domains, with an affinity comparable to SIM-SUMO1 interaction. The study also unraveled specific residues involved in the interaction of AGO2 with miRNA-loading components such as Dicer and HSP90. Collectively, the results support the conclusion that multiple SIMs contribute to the association of Nup358 with AGO2.

摘要

Micro-RNA 介导的 mRNA 翻译抑制代表了转录后基因表达的主要调控模式。最近,核孔蛋白 Nup358 被证明与 AGO 蛋白相互作用,AGO 蛋白是 miRNA 诱导的沉默复合物(miRISC)的关键组成部分,并促进 miRISC 与靶 mRNA 的偶联。先前的结果表明,Nup358 上存在的 SUMO 相互作用基序(SIM)介导与 AGO 蛋白的相互作用。在这里,我们表明 Nup358-SIM 在 AGO2 上具有多个相互作用区域,特别是在 N、PAZ 和 MID 结构域内,与 SIM-SUMO1 相互作用的亲和力相当。该研究还揭示了特定残基参与了 AGO2 与 miRNA 加载成分(如 Dicer 和 HSP90)的相互作用。总之,这些结果支持了这样的结论,即多个 SIM 有助于 Nup358 与 AGO2 的结合。

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