Abstract PR05: Regulation of mRNA N6-adenosine methylation by the mTOR signaling

N6-adenosine methylation (m6A) is the most abundant chemical modification on eukaryotic mRNA. Emerging evidence shows that alterations in m6A modifications on mRNAs encoding oncogenes and tumor suppressors drive cancer initiation and progression including leukemia, glioma, breast and lung cancers. A methyltransferase complex METTL3/METTL14/WTAP deposits methyl groups on mRNA, and then the m6A-marked mRNAs undergo various fates including changes in stability, localization, and translation efficiency. Through phosphoproteomic and transcriptomic analyses of mTOR signaling, we identified the methyltransferase complex as a novel downstream target of the mTOR pathway. We have also found that mTOR signaling, potentially through m6A methylation, regulates expression of the one-carbon metabolic pathway enzymes, which provide building blocks and methyl donors for growing cells. Together, our results indicate that mTOR signaling controls the activity of the methyltransferase complex to govern the m6A modifications of key mRNAs impacting tumor growth. This abstract is also being presented as Poster A11. Citation Format: Gina Lee, Sungyun Cho, Brian F. Pickering, Cholsoon Jang, Joshua D. Rabinowitz, Samie R. Jaffrey, John Blenis. Regulation of mRNA N6-adenosine methylation by the mTOR signaling [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr PR05.