# Mechanisms of translation regulation by N4-acetylcytidine in cancer cells

> **NIH NIH R00** · NORTHWESTERN UNIVERSITY · 2022 · $249,000

## Abstract

Project Summary/Abstract
Translation of messenger RNAs (mRNA) is commonly dysregulated in cancer cells, highlighting regulatory
mechanisms in translation as potential targets for cancer treatment. Chemical modifications of mRNA, known as
the epitranscriptome, have emerged as a new layer of translation regulation. Yet, the types and prevalence of
mRNA modifications as well as their roles in cancer remain poorly understood. N4-acetylcytidine (ac4C) is a
novel mRNA modification that directly enhances translation efficiency of target mRNAs, representing a new and
significant layer of translational regulation. Of substantial relevance to cancer, the enzyme that catalyzes the
deposition of ac4C, N-acetyltransferase 10 (NAT10), is commonly dysregulated in cancers, whereas NAT10
depletion specifically decreases growth of cancer cells, including acute myeloid leukemia (AML) cells. In light of
these observations, this proposal stipulates that NAT10-catalyzed ac4C promotes proliferation of AML cells by
enhancing translation efficiency. During the K99 phase, this study aims to investigate the molecular mechanisms
of mRNA acetylation (Aim 1) and the mechanisms by which ac4C promotes translation efficiency (Aim 2). In the
R00 phase, this proposal aims to evaluate whether NAT10-catalyzed ac4C promotes AML growth by enhancing
translation of proliferation-promoting factors (Aim 3). The overall long-term goals of this study are to expand our
understanding of the epitranscriptome and the mechanisms that dynamically regulate translation efficiency in
cancer cells, using this knowledge to implement novel therapeutic strategies for human conditions where
translation is altered, including AML and other cancers. My career goal is to develop an independent high-quality
research program for the benefit of human health. To achieve these goals, I built a career development plan
which includes this research proposal and a plan for training, mentoring and networking to expand my research,
bioinformatical, leadership and mentoring skills. The K99 phase will be developed in the Intramural Research
Program of the National Cancer Institute (NCI) and will be mentored by Dr. Shalini Oberdoerffer (NCI), and co-
mentored by Dr. Jeffery Coller (Case Western Reserve University). The NCI Intramural Research Program offers
strong well-established research programs and multiple resources for career development and transition of
postdoctoral fellows.

## Key facts

- **NIH application ID:** 10468324
- **Project number:** 5R00CA245035-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Daniel Arango
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2019-12-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468324

## Citation

> US National Institutes of Health, RePORTER application 10468324, Mechanisms of translation regulation by N4-acetylcytidine in cancer cells (5R00CA245035-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10468324. Licensed CC0.

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