MAPK13 stabilization via m⁶A mRNA modification limits anticancer efficacy of rapamycin.

ABSTRACT: N⁶-adenosine methylation (m⁶A) is the most abundant mRNA modification that controls gene expression through diverse mechanisms. Accordingly, m⁶A-dependent regulation of oncogenes and tumor suppressors contributes to tumor development. However, the role of m⁶A-mediated gene regulation upon drug treatment or resistance is poorly understood. Here, we report that m⁶A modification of mitogen-activated protein kinase 13 (MAPK13) mRNA determines the sensitivity of cancer cells to the mechanistic target of rapamycin complex 1 (mTORC1)-targeting agent rapamycin. mTORC1 induces m⁶A modification of MAPK13 mRNA at its 3' untranslated region through the methyltransferase-like 3 (METTL3)-METTL14-Wilms' tumor 1-associating protein(WTAP) me

SUBMITTER: Kim J 

PROVIDER: S-EPMC10511813 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature