IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation.

ABSTRACT: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal RNA-binding protein and a non-canonical reader of N6-methyladenosine (m⁶A) mRNA modifications, is known to be critical for leukemogenesis. To understand how the oncogenic function of IGF2BP3 impacts metabolism, we performed metabolic profiling and observed changes in glycolytic flux and one-carbon metabolism, including the biosynthesis of S-adenosyl methionine (SAM), a key substrate for methylation reactions within the cell. Using enhanced crosslinking immunoprecipitation (eCLIP) and polyribosome profiling, we found that IGF2BP3 promotes translation of the regulatory subunit of the methionine adenosyltransferase complex (MAT2B), which is involved in SAM production. Remarkably, IGF2BP3 promotes and alters

SUBMITTER: Sharma G 

PROVIDER: S-EPMC12593248 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature