title: Prevalent RNA recognition motif duplication in the human genome.
abstract: The sequence-specific recognition of RNA by proteins is mediated through various RNA binding domains, with the RNA recognition motif (RRM) being the most frequent and present in >50% of RNA-binding proteins (RBPs). Many RBPs contain multiple RRMs, and it is unclear how each RRM contributes to the binding specificity of the entire protein. We found that RRMs within the same RBP (i.e., sibling RRMs) tend to have significantly higher similarity than expected by chance. Sibling RRM pairs from RBPs shared by multiple species tend to have lower similarity than those found only in a single species, suggesting that multiple RRMs within the same protein might arise from domain duplication followed by divergence through random mutations. This finding is exemplified by a recent RRM domain duplication in DAZ proteins and an ancient duplication in PABP proteins. Additionally, we found that different similarities between sibling RRMs are associated with distinct functions of an RBP and that the RBPs tend to contain repetitive sequences with low complexity. Taken together, this study suggests that the number of RBPs with multiple RRMs has expanded in mammals and that the multiple sibling RRMs may recognize similar target motifs in a cooperative manner.
authors.forename: Yihsuan S
authors.initials: YS
authors.lastname: Tsai
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Gomez
authors.forename: Zefeng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D001665:Binding Sites; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D059372:Nucleotide Motifs / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA
keywords: RNA binding proteins; RNA processing; RNA recognition motif; domain duplication