PRPS2 enhances RNA m⁶A methylation by stimulating SAM synthesis through enzyme-dependent and independent mechanisms.

ABSTRACT: Cancer cells exploit altered metabolic pathways to dynamically regulate epigenetic methylation and thus promote tumorigenesis and metastasis. In various human cancers, such as lung adenocarcinoma, the level of a key cellular metabolite, S-adenosylmethionine (SAM), is prominently upregulated for RNA hypermethylation as the methyl donor. However, the specific mechanisms by which cancer cells produce SAM to sustain RNA methylation remain elusive. Here, we demonstrate that PRPS2, a phosphoribosyl pyrophosphate synthetase isoform involved in the first and rate-limiting step of the purine biosynthesis pathway, exhibits distinct oncogenic functionality in regulating RNA methylation, unlike its homolog PRPS1. PRPS2 utilizes four non-conserved key residues to bypass the typical ADP/GDP allosteric f

SUBMITTER: Zhang L 

PROVIDER: S-EPMC12037730 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature