mRNA Targeting to Endoplasmic Reticulum Precedes Ago Protein Interaction and MicroRNA (miRNA)-mediated Translation Repression in Mammalian Cells |
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Authors: | Bahnisikha Barman Suvendra N. Bhattacharyya |
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Affiliation: | From the RNA Biology Research Laboratory, Molecular Genetics Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, 4, Raja S C Mullick Road, Kolkata 700032, India |
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Abstract: | MicroRNA (miRNA) binds to the 3′-UTR of its target mRNAs to repress protein synthesis. Extensive research was done to understand the mechanism of miRNA-mediated repression in animal cells. Considering the progress in understanding the mechanism, information about the subcellular sites of miRNA-mediated repression is surprisingly limited. In this study, using an inducible expression system for an miRNA target message, we have delineated how a target mRNA passes through polysome association and Ago2 interaction steps on rough endoplasmic reticulum (ER) before the miRNA-mediated repression sets in. From this study, de novo formed target mRNA localization to the ER-bound polysomes manifested as the earliest event, which is followed by Ago2 micro-ribonucleoprotein binding, and translation repression of target message. Compartmentalization of this process to rough ER membrane ensures enrichment of miRNA-targeted messages and micro-ribonucleoprotein components on ER upon reaching a steady state. |
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Keywords: | Argonaute endoplasmic reticulum (ER) eukaryotic translation initiation gene expression microRNA (miRNA) mRNA miRNA Polysome Ago2 endoplasmic reticulum translation repression |
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