The identities of sym-2, sym-3 and sym-4, three genes that are synthetically lethal with mec-8 in Caenorhabditis elegans.

On the basis of synthetic lethality, five genes in Caenorhabditis elegans are known to be redundant with the mec-8 gene, which encodes a protein that contains two copies of an RNA recognition motif (RRM) and affects alternative RNA splicing. The molecular identities of two of the redundant genes, sym-1 and sym-5, were previously reported. The remaining three genes have now been cloned, and their synthetically lethal phenotypes with mec-8 are described in more detail. Animals homozygous for mec-8 and sym-2 loss-of-function mutations die during late embryogenesis. The SYM-2 predicted protein contains three RRMs; we propose that SYM-2 and MEC-8 can substitute for each other in promoting the maturation of the transcripts of a vital gene. Animals homozygous for mutations in mec-8 and in either sym-3 or sym-4 have the same striking defect: they arrest development just prior to or just after hatching with a pharynx that appears fully formed but is not properly attached to the body cuticle. sym-3 encodes a protein of unknown function with orthologs in Drosophila and mammals. sym-4 encodes a WD-repeat protein and may also have orthologs in Drosophila and mammals. We propose that SYM-3 and SYM-4 contribute to a common developmental pathway that is redundant with a MEC-8-dependent pathway.