Sahoo , M.R. and Gaikwad , S. and Khuperkar , D. and Ashok, M. and Helen , M. and Yadav , S.K. and Singh , A. and Magre , I. and Deshmukh , P. and Dhanvijay , S. and Sahoo , P.K. and Ramtirtha , Y. and Madhusudhan, M.S. and Gayathri , P. and Seshadri , V. and Joseph , J. (2017) Nup358 binds to AGO proteins through its SUMO-interacting motifs and promotes the association of target mRNA with miRISC. EMBO Report, 18 (2). pp. 241-263. ISSN Volume 18, Issue 2

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Abstract

MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing. However, how miRISC identifies the target mRNA in vivo is not well understood. Here, we show that the nucleoporin Nup358 plays an important role in this process. Nup358 localizes to the nuclear pore complex and to the cytoplasmic annulate lamellae (AL), and these structures dynamically associate with two mRNP granules: processing bodies (P bodies) and stress granules (SGs). Nup358 depletion disrupts P bodies and concomitantly impairs the miRNA pathway. Furthermore, Nup358 interacts with AGO and GW182 proteins and promotes the association of target mRNA with miRISC. A well-characterized SUMO-interacting motif (SIM) in Nup358 is sufficient for Nup358 to directly bind to AGO proteins. Moreover, AGO and PIWI proteins interact with SIMs derived from other SUMO-binding proteins. Our study indicates that Nup358–AGO interaction is important for miRNA-mediated gene silencing and identifies SIM as a new interacting motif for the AGO family of proteins. The findings also support a model wherein the coupling of miRISC with the target mRNA could occur at AL, specialized domains within the ER, and at the nuclear envelope.

Item Type:	Article
Subjects:	Cell Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	24 Apr 2017 06:10
Last Modified:	24 Apr 2017 06:10
URI:	http://nccs.sciencecentral.in/id/eprint/405

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