title: The survival motor neuron gene smn-1 interacts with the U2AF large subunit gene uaf-1 to regulate Caenorhabditis elegans lifespan and motor functions.
abstract: Spinal muscular atrophy (SMA), the most frequent human congenital motor neuron degenerative disease, is caused by loss-of-function mutations in the highly conserved survival motor neuron gene SMN1. Mutations in SMN could affect several molecular processes, among which aberrant pre-mRNA splicing caused by defective snRNP biogenesis is hypothesized as a major cause of SMA. To date little is known about the interactions of SMN with other splicing factor genes and how SMN affects splicing in vivo. The nematode Caenorhabditis elegans carries a single ortholog of SMN, smn-1, and has been used as a model for studying the molecular functions of SMN. We analyzed RNA splicing of reporter genes in an smn-1 deletion mutant and found that smn-1 is required for efficient splicing at weak 3' splice sites. Genetic studies indicate that the defective lifespan and motor functions of the smn-1 deletion mutants could be significantly improved by mutations of the splicing factor U2AF large subunit gene uaf-1. In smn-1 mutants we detected a reduced expression of U1 and U5 snRNAs and an increased expression of U2, U4 and U6 snRNAs. Our study verifies an essential role of smn-1 for RNA splicing in vivo, identifies the uaf-1 gene as a potential genetic modifier of smn-1 mutants, and suggests that SMN-1 has multifaceted effects on the expression of spliceosomal snRNAs.
authors.affiliation: a State Key Laboratory of Medical Genetics; School of Life Sciences ; Central South University ; Changsha , Hunan , China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Gao
authors.forename: Yanling
authors.initials: Y
authors.lastname: Teng
authors.forename: Jintao
authors.initials: J
authors.lastname: Luo
authors.forename: Liange
authors.initials: L
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Zhuohua
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yong-Chao
authors.initials: YC
authors.lastname: Ma
authors.forename: Long
authors.initials: L
authors.lastname: Ma
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism; D000072668:Splicing Factor U2AF; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D009687:Nuclear Proteins; D012322:RNA Precursors; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D000072668:Splicing Factor U2AF; D055533:Survival of Motor Neuron 1 Protein; C000607494:U2AF2 protein, human; C486185:UAF-1 protein, C elegans
keywords: SMA; SMN; U2AF large subunit; smn-1; uaf-1