title: Control of the localization and function of a miRNA silencing component TNRC6A by Argonaute protein.
abstract: GW182 family proteins play important roles in microRNA (miRNA)-mediated RNA silencing. They directly interact with Argonaute (Ago) proteins in processing bodies (P bodies), cytoplasmic foci involved in mRNA degradation and storage. Recently, we revealed that a human GW182 family protein, TNRC6A, is a nuclear-cytoplasmic shuttling protein, and its subcellular localization is regulated by its own nuclear localization signal and nuclear export signal. Regarding the further controlling mechanism of TNRC6A subcellular localization, we found that TNRC6A protein is tethered in P bodies by direct interaction with Ago2 under Ago2 overexpression condition in HeLa cells. Furthermore, it was revealed that such Ago proteins might be strongly tethered in the P bodies through Ago-bound small RNAs. Thus, our results indicate that TNRC6A subcellular localization is substantially controlled by the interaction with Ago proteins. Furthermore, it was also revealed that the TNRC6A subcellular localization affects the RNA silencing activity.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nishi
authors.affiliation: Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Suzawa
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyakawa
authors.affiliation: Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nagasawa
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba-ken 277-8651, Japan.
authors.forename: Yvelt
authors.initials: Y
authors.lastname: Ming
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tanokura
authors.affiliation: Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba-ken 277-8651, Japan ktei@bs.s.u-tokyo.ac.jp.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ui-Tei
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D060565:Argonaute Proteins / Q000378:metabolism*; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009154:Mutation; D034622:RNA Interference; D058727:RNA, Small Untranslated / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D001324:Autoantigens; D035683:MicroRNAs; D058727:RNA, Small Untranslated; D016601:RNA-Binding Proteins; C465663:TNRC6A protein, human