The elongator (ELP) complex consisting of Elp1-6p has been indicated to play roles in multiple cellular processes. In yeast, the ELP complex has been shown to genetically interact with Uba4p/Urm1p and Kti11-13p for a function in tRNA modification. Through a Caenorhabditis elegans genetic suppressor screen and positional cloning, we discovered that loss-of-function mutations of
moc-3 and
dph-3, orthologs of the yeast UBA4 and KTI11, respectively, effectively suppress the Multivulva (Muv) phenotype of the
lin-1(
e1275, R175Opal) mutation. These mutations do not suppress the Muv phenotype caused by other
lin-1 alleles or by gain-of-function alleles of ras or raf that act upstream of
lin-1. The suppression can also be reverted by RNA interference of
lin-1. Furthermore, we showed that
dph-3(lf) also suppressed the defect of
lin-1(
e1275) in promoting the expression of a downstream target (
egl-17). These results indicate that suppression by the
moc-3 and
dph-3 mutations is due to the elevated activity of
lin-1(
e1275) itself rather than the altered activity of a factor downstream of
lin-1. We further showed that loss-of-function mutations of
urm-1 and
elpc-1-4, the worm counterparts of URM1 and ELP complex components in yeast, also suppressed
lin-1(
e1275). We also confirmed that
moc-3(lf) and
dph-3(lf) have defects in tRNA modifications as do the mutants of their yeast orthologs. These results, together with the observation of a likely readthrough product from a
lin-1(
e1275)::gfp fusion transgene indicate that the aberrant tRNA modification led to failed recognition of a premature stop codon in
lin-1(
e1275). Our genetic data suggest that the functional interaction of
moc-3/urm-1 and
dph-3 with the ELP complex is an evolutionarily conserved mechanism involved in tRNA functions that are important for accurate translation.