# Elucidating the regulation of RNA methylation by mTOR signaling in cancer

> **NIH NIH K22** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $257,826

## Abstract

PROJECT SUMMARY/ABSTRACT
Over the past decade, our knowledge of RNA chemical modifications such as N6-adenosine methylation (m6A)
on mRNAs has increased due to the development of transcriptome-wide sequencing technologies and several
assays to detect RNA modifications. Emerging evidence shows that alteration of m6A modification on mRNAs
encoding oncogenes and tumor suppressors is linked to cancer development and progression including
leukemia, glioma, breast and lung cancers. These RNA modifications are processed by several RNA binding
proteins such as RNA methyl transferases and demethylases. The expression and activities of these enzymes
are likely to be modulated by upstream signaling pathways during tumorigenesis, however, our understanding
of how signal transduction pathway controls these enzymes and the consequent RNA modifications is still
rudimentary. Through phosphoproteomic and transcriptomic analysis of the mTOR signaling pathway, I have
identified links between the mTOR signaling and enzymes that regulate m6A RNA methylation. My working
hypothesis, which is supported by preliminary data, is that mTOR pathway, by regulating the expression and
activities of m6A methyl transferase complex, controls mRNA metabolism. More importantly, my data suggest
that this mTOR-m6A signaling regulates the expression of enzymes involved in one-carbon metabolism, a
metabolic pathway required for high proliferation rate and survival of cancer cells. The proposed experimental
strategies will reveal how mTOR signaling controls expression of oncogenes and tumor suppressors through
RNA methylation, and its connection to one-carbon metabolism in cancer. Successful completion of this
proposal will provide a rationale for the characterization of new cancer biomarkers and therapeutics targeting
RNA methylation process downstream of oncogenic signaling pathways.

## Key facts

- **NIH application ID:** 10693796
- **Project number:** 5K22CA234399-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Gina Lee
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $257,826
- **Award type:** 5
- **Project period:** 2022-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693796

## Citation

> US National Institutes of Health, RePORTER application 10693796, Elucidating the regulation of RNA methylation by mTOR signaling in cancer (5K22CA234399-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10693796. Licensed CC0.

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