Worm Breeder's Gazette 12(2): 98 (January 1, 1992)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The six smg genes ( smg-1 through smg-6 )encode products that prevent the accumulation of aberrant mRNAs. Mutations in any of the smg genes allow otherwise unstable aberrant mRNAs to accumulate to near wild -type levels (WBG 11 (5):91). Pulak, De Stasio and Anderson have described specific unc-54 nonsense mutations that are recessive, loss-of-function alleles in smg(+) backgrounds but are dominant, gain-of-function alleles in smg(-) backgrounds (WBG 11(5):92). Specific alleles of several other genes ( dpy-5 , dpy-14 and glp-1 )that are recessive (or only weakly dominant) in a smg(+) background are dominant (or more strongly dominant) in a smg(-) background. It was proposed that these mutations are dominant in smg(-) backgrounds due to the accumulation of nonsense mutant mRNAs which, when translated, yield truncated polypeptides that disrupt some cellular function. Pulak and Anderson (WBG 11(5):91) suggested that the smg gene products comprise a cellular surveillance system that, by degrading aberrant mRNAs, minimize the potentially toxic effects of translating these mutant mRNAs. Although these results concern DNA-based mutations, it was suggested that the smg system protects cells from aberrant mRNAs that result from errors of transcription or mRNA processing. These errors are expected to occur more frequently than DNA lesions in vivo.
We would like to determine if the smg system prevents many different mutations from having dominant effects. If true, this would suggest that many protein fragments are toxic and that mutant hunts in a smg(-) background should reveal novel classes of dominant mutations. To test these hypotheses, we are isolating a collection of dominant visible mutations in a smg(-) background and determining whether these mutations are recessive (or less severely dominant) in a smg(+) background.
To date, we have isolated and characterized 31 independent EMS-induced dominant visible mutations in a smg(-) background. Seventeen of these mutations are recessive in a smg(+) background, and 4 have a less severe dominant phenotype in a smg(+) background. Ten mutants have virtually identical dominant phenotypes in smg(+) and smg(-) backgrounds. Thus, approximately 2/3 of the isolated mutations either require the smg mutation for their dominance or have their dominant phenotype enhanced in a smg(-) background. We have not yet rigorously determined for all mutants the phenotypes of homozygotes in smg(+) and smg(-) backgrounds. However, for the cases tested, the homozygous phenotypes in smg(+) and smg(-) backgrounds appear to be identical.
Of the 21 dominant mutations that are smg-dependent or smg-enhanced, the following phenotypic classes are represented: Curly-Unc (16)-representing at least two genes, 10 map to LGV and 6 to LGX; Kinker-Unc (1); Coiler-Unc (1); Reverse-Unc(1); Sma (1); and Dpy (1). Of the 10 smg-independent mutations we have isolated, the following phenotypic classes are represented: Paralyzed Unc (4); Dpy (2); Shrinker (1); Curly-Unc (1); Coiler-Unc (1); and Kinker-Unc (1).
The number of different phenotypic classes, and presumably genes, that show smg dependence and/or smg-enhancement of dominance suggests: (1) that many different processes are susceptible to toxic fragment polypeptides; (2) that the smg genes protect cells from these toxic fragments by preventing the accumulation of mRNAs that encode them; (3) that mutant hunts in a smg(-) background will identify new classes of mutations, and quite possibly new genes.