title: RNA export factor Ddx19 is required for nuclear import of the SRF coactivator MKL1.
abstract: Controlled transport of macromolecules between the cytoplasm and nucleus is essential for homeostatic regulation of cellular functions. For instance, gene expression entails coordinated nuclear import of transcriptional regulators to activate transcription and nuclear export of the resulting messenger RNAs for cytoplasmic translation. Here we link these two processes by reporting a novel role for the mRNA export factor Ddx19/Dbp5 in nuclear import of MKL1, the signal-responsive transcriptional activator of SRF. We show that Ddx19 is not a general nuclear import factor, and that its specific effect on MKL1 nuclear import is separate from its role in mRNA export. Both helicase and nuclear pore-binding activities of Ddx19 are dispensable for MKL1 nuclear import, but RNA binding is required. Mechanistically, Ddx19 operates by modulating the conformation of MKL1, which affects its interaction with Importin-β for efficient nuclear import. Thus, Ddx19 participates in mRNA export, translation and nuclear import of a key transcriptional regulator.
authors.affiliation: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki, Viikinkaari 9, Helsinki 00014, Finland.
authors.forename: Eeva Kaisa
authors.initials: EK
authors.lastname: Rajakylä
authors.affiliation: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki, Viikinkaari 9, Helsinki 00014, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Viita
authors.affiliation: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki, Viikinkaari 9, Helsinki 00014, Finland.
authors.forename: Salla
authors.initials: S
authors.lastname: Kyheröinen
authors.affiliation: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki, Viikinkaari 9, Helsinki 00014, Finland.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Huet
authors.affiliation: Transcription group, Cancer Research UK London Research Institute, London WC2A 3LY, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Treisman
authors.affiliation: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki, Viikinkaari 9, Helsinki 00014, Finland.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Vartiainen
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012313:RNA / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism
chemical_list: C000604613:DDX19 protein, mouse; C424166:KPNB1 protein, human; C431575:MRTFA protein, human; C511173:Mrtfa protein, mouse; D029543:Nucleocytoplasmic Transport Proteins; D015534:Trans-Activators; D028961:beta Karyopherins; D012313:RNA; C121148:DDX19B protein, human; D053487:DEAD-box RNA Helicases