Methionine depletion induces transcription of the mRNA (N6-adenosine)methyltransferase.

This study examines the genetic expression of the S-adenosyl-L-methionine binding subunit of the mRNA (N6-adenosine)methyltransferase (MT-A70) in cultured cells under conditions known to affect transmethylation reactions. Methionine dependence, disrupted methionine metabolism, and increased transmethylation reactions are all phenotypes characteristic of cancer cells. The results show that both methionine depletion and inhibition of S-adenosyl-L-methionine formation can induce up to a four-fold increase in transcription of this S-adenosyl-L-methionine binding subunit. The two splice-variant mRNAs produced from the MT-A70 gene are transcribed at different rates depending on the level of S-adenosyl-L-methionine inhibition. This result may reflect differing Km values toward the substrate for the different enzyme isoforms. 3-Deazaadenosine, an inhibitor known to block certain mRNA transmethylations, was shown to have no effect on MT-A70 gene expression. This result indicates that the control of MT-A70 gene expression is directly related to methionine availability and the subsequent synthesis of S-adenosyl-L-methionine.