mRNA surveillance mitigates genetic dominance in Caenorhabditis elegans.
Nonsense mutant mRNAs are unstable in all eucaryotes tested, a phenomenon termed nonsense-mediated mRNA decay (NMD) or mRNA surveillance. Functions of the seven smg genes are required for mRNA surveillance in Caenorhabditis elegans. In Smg(+) genetic backgrounds, nonsense-mutant mRNAs are unstable, while in Smg(-) backgrounds such mRNAs are stable. Previous work has demonstrated that the elevated level of nonsense-mutant mRNAs in Smg(-) animals can influence the phenotypic effects of heterozygous nonsense mutations. Certain nonsense alleles of a muscle myosin heavy chain gene are recessive in Smg(+) backgrounds but strongly dominant in Smg(-) backgrounds. Such alleles probably express disruptive myosin polypeptide fragments whose abundance is elevated in smg mutants due to elevation of mRNA levels. We report here that mutations in a variety of C. elegans genes are strongly dominant in Smg(-), but recessive or only weakly dominant in Smg(+) backgrounds. We isolated 32 dominant visible mutations in a Smg(-) genetic background and tested whether their dominance requires a functional NMD system. The dominance of 21 of these mutations is influenced by NMD. We demonstrate, furthermore, that in the case of myosin, the dominant-negative effects of nonsense alleles are likely to be due to expression of N-terminal nonsense-fragment polypeptides, not to mistranslation of the nonsense codons. mRNA surveillance, therefore, may mitigate potentially deleterious effects of many heterozygous germline and somatic nonsense or frame-shift mutations. We also provide evidence that smg-6, a gene previously identified as being required for NMD, performs essential function(s) in addition to its role in NMD.
Cali
B M
BM
Department of Genetics, University of Wisconsin, Madison 53706, USA.
Anderson
P
P
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D005804:Genes, Lethal; D015801:Helminth Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000502:physiology*
D015801:Helminth Proteins; D012333:RNA, Messenger; D018995:Myosin Heavy Chains