title: Phylogenetic and molecular characterization of the splicing factor RBM4.
abstract: The mammalian multi-functional RNA-binding motif 4 (RBM4) protein regulates alterative splicing of precursor mRNAs and thereby affects pancreas and muscle cell differentiation. RBM4 homologs exist in all metazoan lineages. The C-terminal unstructured domain of RBM4 is evolutionarily divergent and contains stretches of low-complexity sequences, including single amino acid and/or dipeptide repeats. Here we examined the splicing activity, phosphorylation potential, and subcellular localization of RBM4 homologs from a wide range of species. The results show that these RBM4 homologs exert different effects on 5' splice site utilization and exon selection, and exhibit different subnuclear localization patterns. Therefore, the C-terminal domain of RBM4 may contribute to functional divergence between homologs. On the other hand, analysis of chimeric human RBM4 proteins containing heterologous sequences at the C-terminus revealed that the N-terminal RNA binding domain of RBM4 could have a dominant role in determining splicing outcome. Finally, all RBM4 homologs examined could be phosphorylated by an SR protein kinase, suggesting that they are regulated by a conserved mechanism in different species. This study offers a first clue to functional evolution of a splicing factor.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Lu
authors.forename: Tz-Hao
authors.initials: TH
authors.lastname: Chen
authors.forename: Jhe-Rong
authors.initials: JR
authors.lastname: Wu
authors.forename: Hung-Hsi
authors.initials: HH
authors.lastname: Chen
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Yu
authors.forename: Woan-Yuh
authors.initials: WY
authors.lastname: Tarn
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D023061:Gene Order; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D029721:Drosophila Proteins; C105214:Lark protein, Drosophila; C473692:RBM4 protein, human; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins