The catalytic efficiency of METTL16 affects cellular processes by governing the intracellular S-adenosylmethionine setpoint.

ABSTRACT: The methyl donor S-adenosylmethionine (SAM) regulates many cellular processes. The N6-methyladenosine (m⁶A) methyltransferase METTL16 regulates the expression of the SAM synthetase MAT2A, but the consequences of this regulation are not well documented. Here, we used a degron and complementation strategy in HCT116 cells to demonstrate that disruption of MAT2A regulation by METTL16 influences SAM-dependent processes including histone methylation, translation, and RNA methylation. We also identify U6 snRNA pseudogenes as METTL16 substrates. Complementation by a catalytically hyperactive METTL16 complements its methyltransferase activities but decreases intracellular SAM concentrations by abrogating MAT2A regulation. Moreover, these cells are hypersensitive to treatment with a MAT2A

SUBMITTER: Flaherty JN 

PROVIDER: S-EPMC12330366 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature