A conserved mechanism for controlling the translation of beta-F1-ATPase mRNA between the fetal liver and cancer cells

To characterize the mechanisms governing the biogenesis of mitochondria in cancer, we studied the mitochondrial phenotype and the mechanisms controlli ng the expression of the beta subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) gene in the rat FAO and AS80D hepatomas, When compared wit h normal adult rat liver, the relative cellular content of the mitochondria l beta-F1-ATPase and glutamate dehydrogenase, as well as of mitochondrial D NA, was severely reduced in both cell lines. A paradoxical increase in the cellular abundance of beta-F1-ATPase mRNA was observed in cancer cells. Run -on transcription assays and the estimation of mRNA half-lives revealed tha t the increased abundance of beta-F1-ATPase mRNA results from the stabiliza tion of the transcript in cancer. In vitro translation assays revealed a sp ecific inhibition of the synthesis of the beta-precursor when translation r eactions were carried out in the presence of extracts derived from cancer c ells. The inhibitory effect was recapitulated using an RNA chimera that con tained the 3'-untranslated region of beta-F1-ATPase mRNA. Hepatoma extracts also contained an increased activity of the developmentally regulated tran slation-inhibitory proteins that bind the 3'-untranslated region of beta-F1 -ATPase mRNA The results indicate that the expression of this gene in hepat oma cells is controlled by the same mechanisms that regulate its expression in the Liver during fetal development.