Eukaryotic mRNAs that contain premature stop codons are degraded more rapid
ly than their wild-type counterparts, a phenomenon termed "nonsense-mediate
d mRNA decay" (NMD) or "mRNA surveillance." Functions of sh previously desc
ribed Caenorhabditis elegans genes, smg-1 through smg-6, are required for N
MD. Whereas nonsense mutant mRNAs are unstable in smg(+) genetic background
s, such mRNAs have normal stability in smg(-) backgrounds. Previous screens
for smg mutations have likely not identified all genes involved in NMD, bu
t efforts to identify additional smg genes are limited by the fact that alm
ost 90% of sing mutations identified in genome-wide screens are alleles of
smg-1, smg-2, or smg-5. We describe a modified screen for smg mutations tha
t precludes isolating alleles of smg-1, sm-2, and smg-5. Using this screen,
we have identified and cloned smg-7, a previously uncharacterized gene tha
t we show is required for NMD. smg-7 is predicted to encode a novel protein
that contains an acidic carboxyl terminus and two probable tetratricopepti
de repeats. We provide evidence that smg-7 is cotranscribed with the previo
usly characterized gene lin-45 and show that null alleles of smg-7 confer a
temperature-sensitive defect in NMD.