S-adenosylmethionine (SAM) is an important metabolite as a methyl-group donor in DNA and histone methylation, tuning regulation of gene expression. Appropriate intracellular SAM levels must be maintained, because methyltransferase reaction rates can be limited by SAM availability. In response to SAM depletion, MAT2A, which encodes a ubiquitous mammalian methionine adenosyltransferase isozyme, was upregulated through mRNA stabilization. SAM-depletion reduced N-methyladenosine (mA) in the 3' UTR of MAT2A. In vitro reactions using recombinant METTL16 revealed multiple, conserved methylation targets in the 3' UTR. Knockdown of METTL16 and the mA reader YTHDC1 abolished SAM-responsive regulation of MAT2A. Mutations of the target adenine sites of METTL16 within the 3' UTR revealed that these mAs were redundantly required for regulation. MAT2A mRNA methylation by METTL16 is read by YTHDC1, and we suggest that this allows cells to monitor and maintain intracellular SAM levels.

Surgical resection is one of the salvage treatment options for local recurrence or residual nasopharyngeal cancer and secondary cancer in the nasopharynx. Because of the anatomical complexity of the nasopharynx, the approach is limited and it is also difficult to secure a sufficient margin. We report a case of radiation-induced sarcoma that occurred 14 years after chemoradiotherapy as the initial treatment for nasopharyngeal cancer. The tumor, which arose from the superior and posterior wall of the nasopharynx, was resected via the transpalatal approach with mandibular swing combined with nasal endoscopy. By inserting instruments from two insertion paths, we obtained a good field of view and operability.Previous reports about salvage surgery for nasopharyngeal malignant tumors have been limited in Japan; this procedure is considered to be a useful approach to the nasopharynx.