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

被引:132
作者
Longman, D
Johnstone, IL
Cáceres, JF
机构
[1] Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
[2] Univ Glasgow, Wellcome Ctr Mol Parasitol, Glasgow G11 6NU, Lanark, Scotland
基金
英国医学研究理事会;
关键词
Caenorhabditis elegans; pre-mRNA splicing; RNA interference; SR proteins;
D O I
10.1093/emboj/19.7.1625
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1625 / 1637
页数:13
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