title: Importin-β facilitates nuclear import of human GW proteins and balances cytoplasmic gene silencing protein levels.
abstract: MicroRNAs (miRNAs) guide Argonaute (Ago) proteins to distinct target mRNAs leading to translational repression and mRNA decay. Ago proteins interact with a member of the GW protein family, referred to as TNRC6A-C in mammals, which coordinate downstream gene-silencing processes. The cytoplasmic functions of TNRC6 and Ago proteins are reasonably well established. Both protein families are found in the nucleus as well. Their detailed nuclear functions, however, remain elusive. Furthermore, it is not clear which import routes Ago and TNRC6 proteins take into the nucleus. Using different nuclear transport assays, we find that Ago as well as TNRC6 proteins shuttle between the cytoplasm and the nucleus. While import receptors might function redundantly to transport Ago2, we demonstrate that TNRC6 proteins are imported by the Importin-β pathway. Finally, we show that nuclear localization of both Ago2 and TNRC6 proteins can depend on each other suggesting actively balanced cytoplasmic Ago - TNRC6 levels.
authors.affiliation: Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schraivogel
authors.affiliation: Institute of Physiology, Center for Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
authors.forename: Susann G
authors.initials: SG
authors.lastname: Schindler
authors.affiliation: Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Danner
authors.affiliation: Institute of Molecular Immunology, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Marchioninistraße 25, 81377 Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.affiliation: Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Pfaff
authors.affiliation: Intana Biosciences GmbH, Lochhamerstrasse 29A, 82152 Martinsried/Planegg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hannus
authors.affiliation: Institute of Physiology, Center for Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Depping
authors.affiliation: Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany gunter.meister@ur.de.
authors.forename: Gunter
authors.initials: G
authors.lastname: Meister
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D016601:RNA-Binding Proteins / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism*
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D001324:Autoantigens; D016601:RNA-Binding Proteins; C465663:TNRC6A protein, human; D028961:beta Karyopherins