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

Nucleic Acids Res. 2014 Sep;42(15):10173-84. doi: 10.1093/nar/gku692. Epub 2014 Jul 26.


In vertebrates, smooth muscle cells (SMCs) can reversibly switch between contractile and proliferative phenotypes. This involves various molecular mechanisms to reactivate developmental signaling 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-R-E-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 paralogs in vertebrates and in its insect and worm orthologs (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 translational elongation eEF2 protein, to upregulate NOGGIN 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • HEK293 Cells
  • Humans
  • Leucine / chemistry
  • Models, Molecular
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Protein Multimerization
  • RNA-Binding Proteins / chemistry*


  • RBPMS2 protein, human
  • RNA-Binding Proteins
  • Leucine

Associated data

  • PDB/2M9K