title: Complex evolutionary relationships among four classes of modular RNA-binding splicing regulators in eukaryotes: the hnRNP, SR, ELAV-like and CELF proteins.
abstract: Alternative RNA splicing in multicellular organisms is regulated by a large group of proteins of mainly unknown origin. To predict the functions of these proteins, classification of their domains at the sequence and structural level is necessary. We have focused on four groups of splicing regulators, the heterogeneous nuclear ribonucleoprotein (hnRNP), serine-arginine (SR), embryonic lethal, abnormal vision (ELAV)-like, and CUG-BP and ETR-like factor (CELF) proteins, that show increasing diversity among metazoa. Sequence and phylogenetic analyses were used to obtain a broader understanding of their evolutionary relationships. Surprisingly, when we characterised sequence similarities across full-length sequences and conserved domains of ten metazoan species, we found some hnRNPs were more closely related to SR, ELAV-like and CELF proteins than to other hnRNPs. Phylogenetic analyses and the distribution of the RRM domains suggest that these proteins diversified before the last common ancestor of the metazoans studied here through domain acquisition and duplication to create genes of mixed evolutionary origin. We propose that these proteins were derived independently rather than through the expansion of a single protein family. Our results highlight inconsistencies in the current classification system for these regulators, which does not adequately reflect their evolutionary relationships, and suggests that a domain-based classification scheme may have more utility.
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia. henry.tang@uq.edu.au
authors.forename: Yue Hang
authors.initials: YH
authors.lastname: Tang
authors.forename: Siew Ping
authors.initials: SP
authors.lastname: Han
authors.forename: Karin S
authors.initials: KS
authors.lastname: Kassahn
authors.forename: Adam
authors.initials: A
authors.lastname: Skarshewski
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Rothnagel
authors.forename: Ross
authors.initials: R
authors.lastname: Smith
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000737:chemistry / Q000235:genetics; D016000:Cluster Analysis; D019295:Computational Biology; D016384:Consensus Sequence; D051959:ELAV Proteins / Q000737:chemistry / Q000235:genetics; D056890:Eukaryota / Q000235:genetics*; D019143:Evolution, Molecular; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D010802:Phylogeny; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000235:genetics*; D016415:Sequence Alignment; D000068103:Serine-Arginine Splicing Factors
chemical_list: D051959:ELAV Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D051743:CCAAT-Enhancer-Binding Protein-delta; D000068103:Serine-Arginine Splicing Factors