Functional characterization of SR and SR-related genes in Caenorhabditis elegans

The SR proteins constitute a family of nuclear phosphoproteins, which are r equired for constitutive splicing and also influence alternative splicing r egulation. Initially, it was suggested that SR proteins were functionally r edundant in constitutive splicing. However, differences have been observed in alternative splicing regulation, suggesting unique functions for individ ual SR proteins. Homology searches of the Caenorhabditis elegans genome ide ntified seven genes encoding putative orthologues of the human factors SF2/ ASF, SRp20, SC35, SRp40, SRp75 and p54, and also several SR-related genes, To address the issue of functional redundancy, we used dsRNA interference ( RNAi) to inhibit specific SR protein function during C. elegans development . RNAi with CeSF2/ASF caused late embryonic lethality, suggesting that this gene has an essential function during C. elegans development, RNAi with ot her SR genes resulted in no obvious phenotype, which is indicative of gene redundancy. Simultaneous interference of two or more SR proteins in certain combinations caused lethality or other developmental defects. RNAi with Ce SRPK, an SR protein kinase, resulted in early embryonic lethality, suggesti ng an essential role for SR protein phosphorylation during development.