Maintenance of osmotic homeostasis is one of the most aggressively defended homeostatic setpoints in physiology. One major mechanism of osmotic homeostasis involves the upregulation of proteins that catalyze the accumulation of solutes called organic osmolytes. To better understand how osmolyte accumulation proteins are regulated, we conducted a forward genetic screen in C. elegans for mutants with no induction of osmolyte biosynthesis gene expression (Nio mutants). The
nio-3 mutant encoded a missense mutation in
cpf-2/CstF64 while the
nio-7 mutant encoded a missense mutation in
symk-1/Symplekin. Both
cpf-2 and
symk-1 are nuclear components of the highly conserved 3' mRNA cleavage and polyadenylation complex.
cpf-2 and
symk-1 block the hypertonic induction of
gpdh-1 and other osmotically induced mRNAs, suggesting they act at the transcriptional level. We generated a functional auxin-inducible degron (AID) allele for
symk-1 and found that acute, post-developmental degradation in the intestine and hypodermis was sufficient to cause the Nio phenotype.
symk-1 and
cpf-2 exhibit genetic interactions that strongly suggest they function through alterations in 3' mRNA cleavage and/or alternative polyadenylation. Consistent with this hypothesis, we find that inhibition of several other components of the mRNA cleavage complex also cause a Nio phenotype.
cpf-2 and
symk-1 specifically affect the osmotic stress response since heat shock-induced upregulation of a
hsp-16.2::GFP reporter is normal in these mutants. Our data suggest a model in which alternative polyadenylation of one or more mRNAs is essential to regulate the hypertonic stress response.