| Literature DB >> 28039207 |
Manas Ranjan Sahoo1, Swati Gaikwad1, Deepak Khuperkar1, Maitreyi Ashok1, Mary Helen1, Santosh Kumar Yadav1, Aditi Singh1, Indrasen Magre1, Prachi Deshmukh1, Supriya Dhanvijay1, Pabitra Kumar Sahoo1, Yogendra Ramtirtha2, Mallur Srivatsan Madhusudhan2, Pananghat Gayathri2, Vasudevan Seshadri1, Jomon Joseph3.
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.Entities:
Keywords: Argonaute; Nup358; annulate lamellae; miRNA; nucleoporin
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Year: 2016 PMID: 28039207 PMCID: PMC5286382 DOI: 10.15252/embr.201642386
Source DB: PubMed Journal: EMBO Rep ISSN: 1469-221X Impact factor: 8.807