Phylogenetic and molecular characterization of the splicing factor RBM4.

Chia-Chen Lu, Tz-Hao Chen, Jhe-Rong Wu, Hung-Hsi Chen, Hsin-Yi Yu, Woan-Yuh Tarn

PloS one 2013

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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.

Citation

Chia-Chen Lu, Tz-Hao Chen, Jhe-Rong Wu, Hung-Hsi Chen, Hsin-Yi Yu, Woan-Yuh Tarn. Phylogenetic and molecular characterization of the splicing factor RBM4. PloS one. 2013;8(3):e59092