# Investigating the coordinated interplay of mRNA and tRNA modifications mediated by the FTO-TRMT10A complex

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2021 · $41,730

## Abstract

Project Summary/Abstract
RNA modifications are concurrently found on nearly all RNA species and can dramatically alter the properties
and expression of RNA. Modifications to mRNA can affect gene expression through several mechanisms such
as localization, stability, and translation efficiency. Modifications to tRNAs are known to affect their stability and
abundance as well as their decoding and elongation dynamics during translation. Dysregulation of many
enzyme-mediated RNA modifications have been causally linked to impaired neurological development,
intellectual disabilities, and behavioral abnormalities. There has been a great effort by the field to understand
the functional impact of individual modifications in isolated RNAs, but the interplay of both mRNA and tRNA
modifications has never been explored. The potential for cross-talk between modifications and RNA species
echoes the combinatorial control seen in post-translational modifications. We have recently discovered that two
distinct RNA-modifying enzymes, tRNA methyltransferase 10A (TRMT10A) and the mRNA demethylase Fat
Mass and Obesity protein (FTO), interact and function together to control gene expression. These findings may
represent a novel coregulatory mode of gene regulation accomplished by the coordinated RNA-modifying
activity of TRMT10A and FTO. In order to better understand the functional role of this enzyme complex, we will
(1) define the biochemical and structural parameters of this RNA-modifying complex and (2) elucidate which
mechanism(s) underlie how gene expression is modulated by the activity of FTO-TRMT10A. The first goal will
take advantage of the array of biophysical tools and expertise available to the Department of Biochemistry and
Biophysics to obtain detailed molecular and structural characteristics of wild-type and mutant FTO-TRMT10A
complexes. The second goal will be accomplished by employing a spectrum of molecular biology and
biochemistry techniques in relevant cell lines to analyze RNA subcellular localization, stability, and modification
profile changes. UPenn is an exceptional environment to support my training and this study, fostering a
particularly collaborative campus of researchers that cross many intellectual and technical fields. The countless
opportunities to learn techniques, use specialized equipment, form collaborations, and share ideas will
continue to enrich my research and training. Overall, the tools, training, and expertise are all in place to
successfully accomplish the goals set in this proposed study of the novel coregulation of mRNA and tRNA
modifications.

## Key facts

- **NIH application ID:** 10252781
- **Project number:** 5F31GM139325-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Robert Jordan Ontiveros
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $41,730
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10252781

## Citation

> US National Institutes of Health, RePORTER application 10252781, Investigating the coordinated interplay of mRNA and tRNA modifications mediated by the FTO-TRMT10A complex (5F31GM139325-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10252781. Licensed CC0.

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