# Epitranscriptomic control of ROS

> **NIH NIH R15** · SUNY POLYTECHNIC INSTITUTE · 2022 · $459,347

## Abstract

Maintenance of the GSH redox cycle is reliant on the activities of selenocysteine-containing GSH
metabolizing enzymes which play fundamental roles in chemoprevention. Selenocysteine is the 21st
amino acid and does not contain a dedicated codon. Selenocysteine incorporation during translation
requires UGA-stop-codon recoding, which uses specifically modified tRNA for accurate decoding.
Dynamic changes in tRNA modification are an epitranscriptomic signal because they regulate gene
expression post-transcriptionally. We have shown that the stress-induced translation of many
selenocysteine containing ROS detoxifying enzymes is dependent on the Alkbh8 tRNA
methyltransferase. Alkbh8 enzymatically methylates the uridine wobble base on tRNASelenocysteine to
promote UGA-stop codon decoding. We have developed an Alkbh8 deficient mouse and have used
molecular, biochemical, and genomic approaches to demonstrate that Alkbh8Def mouse embryonic
fibroblasts (MEFs) and some organs display markers of senescence and a senescence gene signature.
Using human cells and our new Alkbh8Def/p16-3MR mice we propose to test the hypothesis that
senescence occurs in vitro and in vivo because of defective epitranscriptomic signals that
controls selenocysteine utilization. To achieve this two aims will: 1. determine if Alkbh8 and other
epitranscriptomic writers that limit selenocysteine utilization restrict the senescence program and 2.
determine if Alkbh8-deficiency drives senescence in vivo and whether senescence ablation accelerates
or tempers pathologies that accompany selenoprotein loss. Our proposal is being submitted with
significant preliminary data supporting the idea that Alkbh8 and epitranscriptomic signals are key to
chemoprevention by limiting senescent activity.

## Key facts

- **NIH application ID:** 10523266
- **Project number:** 1R15CA274603-01
- **Recipient organization:** SUNY POLYTECHNIC INSTITUTE
- **Principal Investigator:** Michael Carpenter
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $459,347
- **Award type:** 1
- **Project period:** 2022-08-24 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10523266

## Citation

> US National Institutes of Health, RePORTER application 10523266, Epitranscriptomic control of ROS (1R15CA274603-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10523266. Licensed CC0.

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