Functional overlap between the mec-8 gene and five sym genes in Caenorhabditis elegans.
Earlier work showed that the Caenorhabditis elegans gene mec-8 encodes a regulator of alternative RNA splicing and that mec-8 null mutants have defects in sensory neurons and body muscle attachment but are generally viable and fertile. We have used a genetic screen to identify five mutations in four genes, sym-1-sym-4, that are synthetically lethal with mec-8 loss-of-function mutations. The phenotypes of sym single mutants are essentially wild type. mec-8; sym-1 embryos arrest during embryonic elongation and exhibit defects in the attachment of body muscle to extracellular cuticle. sym-1 can encode a protein containing a signal sequence and 15 contiguous leucine-rich repeats. A fusion of sym-1 and the gene for green fluorescent protein rescued the synthetic lethality of mec-8; sym-1 mutants; the fusion protein was secreted from the apical hypodermal surface of the embryo. We propose that SYM-1 helps to attach body muscle to the extracellular cuticle and that another gene that is dependent upon mec-8 for pre-mRNA processing overlaps functionally with sym-1. RNA-mediated interference experiments indicated that a close relative of sym-1 functionally overlaps both sym-1 and mec-8 in affecting muscle attachment. sym-2, sym-3, and sym-4 appear to provide additional functions that are essential in the absence of mec-8(+).
Davies
A G
AG
Department of Genetics and Cell Biology, University of Minnesota, St. Paul, Minnesota 55108, USA.
Spike
C A
CA
Shaw
J E
JE
Herman
R K
RK
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D012734:Disorders of Sex Development; D017238:Genes, Helminth / Q000235:genetics / Q000502:physiology*; D005816:Genetic Complementation Test; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D021382:Protein Sorting Signals / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011509:Proteoglycans; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C121973:Sym-1 protein, C elegans; C099356:mec-8 protein, C elegans; C082396:unc-52 protein, C elegans