National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
Division of Biology, Indian Institute of Science Education and Research, Pune, India.
Biochem Biophys Res Commun. 2021 Jun 4;556:45-52. doi: 10.1016/j.bbrc.2021.03.140. Epub 2021 Apr 7.
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.
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。