Spatiotemporal Uncoupling of MicroRNA-Mediated Translational Repression and Target RNA Degradation Controls MicroRNP Recycling in Mammalian Cells

Bose, Mainak and Barman, Bahnisikha and Goswami, Avijit and Bhattacharyya, Suvendra Nath (2017) Spatiotemporal Uncoupling of MicroRNA-Mediated Translational Repression and Target RNA Degradation Controls MicroRNP Recycling in Mammalian Cells. Molecular and Cellular Biology, 37 (4). e00464-16.

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    Abstract

    MicroRNA (miRNA)-mediated repression controls expression of more than half of protein-coding genes in metazoan animals. Translation repression is associated with target mRNA degradation initiated by decapping and deadenylation of the repressed mRNAs. Earlier evidence suggests the endoplasmic reticulum (ER) as the site where microRNPs (miRNPs) interact with their targets before translation repression sets in, but the subcellular location of subsequent degradation of miRNArepressed messages is largely unidentified. Here, we explore the subcellular distribution of essential components of degradation machineries of miRNA-targeted mRNAs. We have noted that interaction of target mRNAs with AGO2 protein on the ER precedes the relocalization of repressed messages to multivesicular bodies (MVBs). The repressed messages subsequently get deadenylated, lose their interaction with AGO2, and become decapped. Blocking maturation of endosomes to late endosome and MVBs by targeting the endosomal protein HRS uncouples miRNA-mediated translation repression from target RNA degradation. HRS is also targeted by the intracellular parasite Leishmania donovani, which curtails the HRS level in infected cells to prevent uncoupling of mRNA-AGO2 interaction, preventing degradation of translationally repressed messages, and thus stops recycling of miRNPs preengaged in repression

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/2657
    Subjects: Molecular & Human Genetics
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 17 May 2017 11:25
    Last Modified: 17 May 2017 11:25
    Official URL: https://doi.org/10.1128/MCB.00464-16.
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