title: Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus.
abstract: GW182 family proteins play important roles in microRNA (miRNA)-mediated gene silencing. They interact with Argonaute (Ago) proteins and localize in processing bodies, which are cytoplasmic foci involved in mRNA degradation and storage. Here, we demonstrated that human GW182 paralog, TNRC6A, is a nuclear-cytoplasmic shuttling protein, and its subcellular localization is conducted by a nuclear export signal (NES) and a nuclear localization signal (NLS) identified in this study. TNRC6A with mutations in its NES region was predominantly localized in the nucleus in an Ago-independent manner. However, it was found that TNRC6A could bring Ago protein into the nucleus via its Ago-interacting motif(s). Furthermore, miRNAs were also colocalized with nuclear TNRC6A-Ago and exhibited gene silencing activity. These results proposed the possibility that TNRC6A plays an important role in navigating Ago protein into the nucleus to lead miRNA-mediated gene silencing.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nishi
authors.forename: Ai
authors.initials: A
authors.lastname: Nishi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ui-Tei
mesh_terms: D020816:Amino Acid Motifs; D060565:Argonaute Proteins / Q000378:metabolism*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009154:Mutation; D049790:Nuclear Export Signals / Q000235:genetics / Q000502:physiology; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D060565:Argonaute Proteins; D001324:Autoantigens; D035683:MicroRNAs; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; C465663:TNRC6A protein, human