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Homodimerization of RBPMS2 through a new RRM-interaction motif is necessary to control smooth muscle plasticity

Abstract : In vertebrates, smooth muscle cells (SMCs) can reversibly switch between contractile and prolifer-ative phenotypes. This involves various molecular mechanisms to reactivate developmental signal-ing pathways and induce cell dedifferentiation. The protein RBPMS2 regulates early development and plasticity of digestive SMCs by inhibiting the bone morphogenetic protein pathway through its interaction with NOGGIN mRNA. RBPMS2 contains only one RNA recognition motif (RRM) while this motif is often repeated in tandem or associated with other functional domains in RRM-containing proteins. Herein, we show using an extensive combination of structure/function analyses that RBPMS2 homodimerizes through a particular sequence motif (D-x-K-x-RE -L-Y-L-L-F: residues 39-51) located in its RRM domain. We also show that this specific motif is conserved among its homologs and par-alogs in vertebrates and in its insect and worm or-thologs (CPO and MEC-8, respectively) suggesting a conserved molecular mechanism of action. Inhibition of the dimerization process through targeting a conserved leucine inside of this motif abolishes the capacity of RBPMS2 to interact with the trans-lational elongation eEF2 protein, to upregulate NOG-GIN mRNA in vivo and to drive SMC dedifferentiation. Our study demonstrates that RBPMS2 possesses an RRM domain harboring both RNA-binding and protein-binding properties and that the newly identified RRM-homodimerization motif is crucial for the function of RBPMS2 at the cell and tissue levels.
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Soumis le : mercredi 15 avril 2020 - 15:07:26
Dernière modification le : mardi 21 avril 2020 - 15:17:39


Sagnol et al - 2014.pdf
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Sébastien Sagnol, Yinshan Yang, Yannick Bessin, Frédéric Allemand, Ilona Hapkova, et al.. Homodimerization of RBPMS2 through a new RRM-interaction motif is necessary to control smooth muscle plasticity. Nucleic Acids Research, Oxford University Press, 2014, ⟨10.1093/nar/gku692⟩. ⟨hal-02543654⟩



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