Human fatty acid synthase mRNA: Tissue distribution, genetic mapping, and kinetics of decay after glucose deprivation

To better understand the accelerated decay of fatty acid synthase (FAS) message that occurs after glucose deprivation (J. Biol. Chem. 1993. 268: 6961-6970), we characterized the 3' terminus of the human message and the kinetics of FAS mRNA decay in HepG2 cells. The FAS gene was localized to human chromosome 17q24-25 and to syntenic distal mouse chromosome 11. Expression of the FAS message in human tissues was ubiquitous with high levels in liver, lung, and intra-abdominal adipose tissue. The 806 nucleotide 3' untranslated region of the human mRNA contained two regions with the instability pentamer AUUUA. Unlike short-lived messages containing AUUUA motifs, FAS mRNA decay after glucose deprivation was not first order, and there were no detectable changes in the poly(A) tail. Glucose deprivation transiently caused FAS message to sediment more rapidly than control message in density gradients. In vivo treatment with different translational inhibitors showed that translation per se was not necessary for FAS mRNA decay; association of polysomes with FAS message protected it from decay. In cell-free decay experiments, FAS mRNA decay was more rapid using components from glucose-deprived than glucose-treated cells. These data suggest that glucose regulates cytoplasmic HepG2 FAS mRNA stability by partitioning the message between a translated pool not subject to degradation and a decay compartment, features reminiscent of regulated stability for other diet- responsive messages.