Functional characterization of SR and SR-related genes in Caenorhabditis elegans.
The SR proteins constitute a family of nuclear phosphoproteins, which are required for constitutive splicing and also influence alternative splicing regulation. Initially, it was suggested that SR proteins were functionally redundant in constitutive splicing. However, differences have been observed in alternative splicing regulation, suggesting unique functions for individual SR proteins. Homology searches of the Caenorhabditis elegans genome identified 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 other 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 CeSRPK, an SR protein kinase, resulted in early embryonic lethality, suggesting an essential role for SR protein phosphorylation during development.
Longman
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MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU.
Johnstone
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IL
Cáceres
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JF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012326:RNA Splicing; D018510:RNA, Helminth / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000068103:Serine-Arginine Splicing Factors
D017931:DNA Primers; D015801:Helminth Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D018510:RNA, Helminth; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000068103:Serine-Arginine Splicing Factors