Loss-of-function mutations in
mec-8, which encodes a putative RNA-binding protein that is required for alternative RNA splicing of the
unc-52 gene, confer mechanosensory and chemosensory defects but do not cause extensive lethality. The combination of a
mec-8 loss-of-function mutation, however, with a viable mutation in any of five sym (synthetic lethal with
mec-8) genes (or with a viable allele of
unc-52, the prototype analysis for this study) results in highly penetrant embryonic or early larval lethality. The molecular identities of
sym-1 and
sym-2 have been previously described [Davies et al. (1999) Genetics 153: 117; Yochem et al. (2001) IWM abstract #1090].The identities of
sym-3 and
sym-4 are now known.
sym-3 corresponds to C54H2.1, which encodes a protein of unknown function. The amino-terminal half is highly similar to a protein predicted from the Drosophila and human genome projects. The
sym-3(
mn618) mutation is in the final splice site.
sym-4 corresponds to R03E1.1, which encodes a large protein with WD repeats. The
sym-4(
mn619) mutation changes a leucine to a glutamine in the third WD repeat. The carboxyl-terminal half of SYM-4 contains the WD repeats and resembles a WD protein of unknown function in Drosophila and humans. The third WD repeats of these proteins, including the leucine that is altered by
mn619, are especially well conserved. The phenotype of the
mec-8;
sym-3 double mutant closely resembles that of the
mec-8;
sym-4 double. The mutants arrest growth as either late-stage embryos or L1 larvae. In either case, the pharynx, which is overtly normal in morphology, is not attached to the outer cuticle, and the larvae therefore cannot feed. The similarity in phenotype raises the possibility that SYM-3 and SYM-4 act in a pathway that is redundant with a pathway that requires MEC-8 for proper splicing of one of its components. Consistent with this hypothesis, the
sym-3(
mn618)
sym-4(
mn619) double mutant is indistinguishable from either single mutant [Davies et al. (1999)].