title: mRNA Targeting to Endoplasmic Reticulum Precedes Ago Protein Interaction and MicroRNA (miRNA)-mediated Translation Repression in Mammalian Cells.
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.
authors: 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.
authors: Bahnisikha
authors: B
authors: Barman
authors: 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 suvendra@iicb.res.in sb@csiriicb.in.
authors: Suvendra N
authors: SN
authors: Bhattacharyya
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011132:Polyribosomes / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics*; D021381:Protein Transport; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C466422:AGO2 protein, human; C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Ago2; Argonaute; Polysome; endoplasmic reticulum; endoplasmic reticulum (ER); eukaryotic translation initiation; gene expression; mRNA; miRNA; microRNA (miRNA); translation repression