FoxA factors are critical regulators of embryonic development and post-embryonic life. C. elegans
pha-4 encodes a FoxA transcription factor that is required to establish the foregut in embryos, and to control growth and longevity after birth (1). Loss of
pha-4 causes severe defects in organogenesis and mis-expression of PHA-4 induces ectopic foregut cells (1). These data show that regulation of
pha-4/Foxa is critical for normal development, but little is known about the regulation of FoxA proteins in any animal. We conducted a genetic screen to identify mutations that can suppress a partial loss of
pha-4 function and identified the AAA+ ATPase homologue
ruvb-1 (2). We have found that
ruvb-1 is a component of the TOR pathway. The most striking phenotype associated with
ruvb-1 homozygous mutants is an arrest during the third larval stage. Previous studies had found that mutations that disrupt insulin signaling (
daf-2/insR), and the TOR kinase pathway (
let-363/TOR,
daf-15/raptor), lead to a dauer or L3 arrest (3).
ruvb-1 larvae lack phenotypes typically associated with
daf-2/insR mutants and are similar to those of
let-363/TOR animals. Both
ruvb-1 and
let-363/TOR control nucleolar size and promote localization of box C/D snoRNPs to nucleoli, suggesting a role in rRNA maturation. Similar to
ruvb-1, inactivation of
let-363/TOR suppressed the lethality associated with reduced
pha-4. The TOR pathway controls protein homeostasis and also contributes to longevity (4). Reduced TOR extends lifespan independent of insulin signaling and does not require
daf-16/Foxo (5,6,7). We find that
pha-4 is required to extend adult lifespan in response to reduced TOR signaling, and our data reveal that regulation of lifespan by TOR does not simply reflect changes in protein biosynthesis. The data suggest that
pha-4 and the TOR pathway antagonize one another to control post-embryonic development and adult longevity.