IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation
Year: 2025
Type: article
Abstract: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal RNA-binding protein and a non-canonical reader of N6-methyladenosine (m 6 A) 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 the level and pattern of m 6 A modifications on mRNA. Taken together, these data suggest the intriguing hypothesis that IGF2BP3 rewrites the epitranscriptome in leukemia cells. Furthermore, this work highlights an interconnection between oncogenic metabolism and RNA modifications, suggesting that pervasive gene expression changes necessary for oncogenesis may be perpetuated by post-transcriptional gene regulation.
Source: Cell Reports
Authors: Gunjan Sharma, Martin Gutierrez, Anthony E. Jones, Shruti Kapoor, Amit Kumar Jaiswal, Zachary T. Neeb, Amy Rios, Poornima Dorairaj, Michelle L. Thaxton, Tasha L. Lin, Tiffany M. Tran, Lyna E.S. Kabbani, Alexander J. Ritter, Georgia M. Scherer, Jacob P. Sorrentino, Linsey Stiles, Johanna ten Hoeve, Robert D. Damoiseaux, Neil K. Garg, Ajit S. Divakaruni, Jeremy R. Sanford, Dinesh S. Rao
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: National Science Foundation, California Institute for Regenerative Medicine, California Institute of Regenerative Medicine, National Institutes of Health, Center for AIDS Research, University of Washington, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Jonsson Comprehensive Cancer Center, Eunice Kennedy Shriver National Institute of Child Health and Human Development, David Geffen School of Medicine, University of California, Los Angeles, UCLA AIDS Institute
Awards: G1100959374, G226708724, G3111867497, Regulation of mRNA isoform fate, G4618448172, Biomedical Data Commons Workbench (BDCW), G6925619362, UCLA Center for AIDS Research (CFAR), G9000090879, G9000091430, A postdoctoral training program for impactful careers in stem cell biology, UCLA Tumor Immunology Institutional Training Grant, Cancer Center Support Grant, Understanding How Metabolic Cofactors Control Cell Function and Fate, Tumor Cell Biology Training Program, Regulation of mRNA Fate
OpenAlex ID: W4414572707