RNA export factor Ddx19 is required for nuclear import of the SRF coactivator MKL1

Eeva Kaisa Rajakylä, Tiina Viita, Salla Kyheröinen, Guillaume Huet, Richard Treisman and Maria K. Vartiainen ()
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Eeva Kaisa Rajakylä: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki
Tiina Viita: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki
Salla Kyheröinen: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki
Guillaume Huet: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki
Richard Treisman: Transcription group, Cancer Research UK London Research Institute
Maria K. Vartiainen: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms6978

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