NAD+-DEPENDENT METHYLENETETRAHYDROFOLATE DEHYDROGENASE-CYCLOHYDROLASE - DETECTION OF THE MESSENGER-RNA IN NORMAL MURINE TISSUE AND TRANSCRIPTIONAL REGULATION OF THE GENE IN CELL-LINES

NAD+-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase, a nuclear-encoded mitochondrial bifunctional enzyme, is detectable in extracts of immortalized and transformed cells but not in most adult tissues (Mejia, N.R. and MacKenzie, R.E. (1985) J. Biol. Chem. 260, 14616-14620). Normal tissues contain low levels of the mRNA, with the exception of thymus and especially testis which contain much higher amounts. The protein could not be detected in any of these normal tissues either by Western analysis or by enzyme activity assay. The elevated level of the mRNA in testis is not dependent on active spermatogenesis. Oncogenic transformation of NIH 3T3 fibroblasts by the Ha-ras oncogene did not significantly affect the steady state level of the dehydrogenase-cyclohydrolase mRNA. The gene in quiescent Balb/c 3T3 fibroblasts is induced by mitogens such as serum and phorbol esters and requires de novo transcription. Post-transcriptionally, the mRNA is stabilized by factors in serum such as insulin-like growth factor-1. The intracellular location of the enzyme and its regulation of expression are consistent with its proposed role in mitochondrial biogenesis.