title: The quaking I-5 protein (QKI-5) has a novel nuclear localization signal and shuttles between the nucleus and the cytoplasm.
abstract: The mouse quaking (qk) gene is essential in both myelination and early embryogenesis. Its product, QKI, is an RNA-binding protein belonging to a growing protein family called STAR (signal transduction and activator of RNA). All members have an approximately 200-amino acid STAR domain, which contains a single extended heteronuclear ribonucleoprotein K homologue domain flanked by two domains called QUA1 and QUA2. We found that QKI isoforms could associate with each other, while one of the lethal mutations qkI(kt4) with a single amino acid change in QUA1 domain, leads to a loss of QKI self-interaction. This suggests that the QUA1 domain is responsible for QKI dimerization. Three QKI isoforms have different carboxyl termini and different subcellular localization. Here, using GFP fusion protein, we identified a 7-amino acid novel nuclear localization sequence in the carboxyl terminus of QKI-5, which is conserved in a subclass of STAR proteins containing SAM68 and ETLE/T-STAR. Thus, we name this motif STAR-NLS. In addition, the effects of active transcription, RNA-binding and self-interaction on QKI-5 localization were analyzed. Furthermore, using an interspecies heterokaryon assay, we found that QKI-5, but not another STAR protein ETLE, shuttles between the nucleus and the cytoplasm, which suggests that QKI-5 functions in both cell compartments.
authors.affiliation: Institute for Cellular and Molecular Biology, Department of Microbiology, University of Texas, Austin, Texas 78712-1064, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: K
authors.initials: K
authors.lastname: Tonissen
authors.forename: R
authors.initials: R
authors.lastname: Tee
authors.forename: K
authors.initials: K
authors.lastname: Artzt
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D019281:Dimerization; D005804:Genes, Lethal; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008164:Luminescent Proteins; D051379:Mice; D008821:Mice, Quaking; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D019913:Nuclear Localization Signals / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D014162:Transfection
chemical_list: D008164:Luminescent Proteins; D019913:Nuclear Localization Signals; C490832:QKI protein, human; C098217:Qk protein, mouse; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins