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| Subject Categories: Cell & Tissue Architecture | RNA |
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| The EMBO Journal
(2006) 25, 1456–1468, doi:10.1038/sj.emboj.7601039 Published online 16 March 2006 |
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| RNA-binding IMPs promote cell adhesion and invadopodia formation |
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| Jonas Vikesaa1, Thomas V O Hansen1, Lars Jønson1, Rehannah Borup1, Ulla M Wewer2, Jan Christiansen3 and Finn C Nielsen1 |
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1 Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2 Department of Molecular Pathology, University of Copenhagen, Copenhagen, Denmark 3 Institute of Molecular Biology and Physiology, University of Copenhagen, Copenhagen, Denmark To whom correspondence should be addressed Finn C Nielsen, Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark. Tel.: +45 3545 2223; Fax: +45 3545 4640; E-mail: fcn@rh.dk Received 28 September 2005; Accepted 17 February 2006; Published online 16 March 2006. |
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| Abstract |
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| Oncofetal RNA-binding IMPs have been implicated in mRNA localization, nuclear export, turnover and translational control. To depict the cellular actions of IMPs, we performed a loss-of-function analysis, which showed that IMPs are necessary for proper cell adhesion, cytoplasmic spreading and invadopodia formation. Loss of IMPs was associated with a coordinate downregulation of mRNAs encoding extracellular matrix and adhesion proteins. The transcripts were present in IMP RNP granules, implying that IMPs were directly involved in the post-transcriptional control of the transcripts. In particular, we show that a 5.0 kb CD44 mRNA contained multiple IMP-binding sites in its 3'UTR, and following IMP depletion this species became unstable. Direct knockdown of the CD44 transcript mimicked the effect of IMPs on invadopodia, and we infer that CD44 mRNA stabilization may be involved in IMP-mediated invadopodia formation. Taken together, our results indicate that RNA-binding proteins exert profound effects on cellular adhesion and invasion during development and cancer formation. |
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| Keywords: CD44, IMP, invadopodia, RNA-binding proteins, RNP granules |
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