Homodimerization of RBPMS2 through a new RRM-interaction motif is necessary to control smooth muscle plasticity.
Bottom Line: 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.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.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.
Affiliation: INSERM U1046, Université Montpellier 1, Université Montpellier 2, 34295 Montpellier, France.Show MeSH
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Mentions: To identify the structural features that are responsible for RBPMS2 function, we analyzed RBPMS2 sequence and its predicted structure. Basic Local Alignment Search Tool (BLAST) searches using human RBPMS2 as a query (NP_919248.1) identified its vertebrate orthologs with high sequence conservation (E-values ranging from 10−153 to 10−114) and also its closely related paralog RBPMS1 (E-values from 10−94 to 10−74) (Figure 1A). This analysis also highlighted the strong similarities of human RBPMS2 and insect CPO (E-values from 10−40 to 10−38) and of both RBPMS2 and CPO sequences with C. elegans MEC-8 (∼10−30). These three proteins were the first RRM-containing proteins detected by BLAST, suggesting a common evolutionary history and some functional homology. Indeed, no other human RNA-binding protein showed such a strong similarity with RBPMS2 (see the snRNP proteins with E-values ∼10−3). Similar results were obtained when we used only the sequence of the RRM domain of RBPMS2, suggesting that RBPMS2, CPO and MEC-8 form an original subfamily of RRM-containing proteins (Figure 1B). This family also includes their paralogs (RBPMS1) that share highly similar RRM sequences in vertebrates. Their common N-terminal RRM domains (90-residue long) share 60–69% of sequence identity. The rest of the sequence showed significant amino acid composition bias toward small and/or polar residues (G, A, S, T, P, Q) and rapid divergence among the closely homologous sequences while no significant similarities could be found with known protein structures. In agreement, disordered segments are predicted by various bioinformatic tools implemented in the meta-server MetaDisorder (32) around the RRM domain (data not shown).
Affiliation: INSERM U1046, Université Montpellier 1, Université Montpellier 2, 34295 Montpellier, France.