# Viral modulation of epitranscriptomic mechanisms

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $580,123

## Abstract

PROJECT SUMMARY
The overall goal of this proposal is to develop high-throughput mass spectrometry technologies applied to the
study of post-transcriptional RNA modifications (PTrMs) and associations with RNA binding proteins (RBPs).
Efficient RNA processing and protein translation requires interactions with numerous RNA binding proteins, and
can be regulated by chemical RNA modifications. PTrMs have been implicated in such diverse processes as
RNA splicing, nuclear export, stability, and translation. The mechanisms by which PTrMs control RNA fate has
opened up a new field dubbed “Epitranscriptomics”. Although there are antibody approaches to detect some
modifications, there is a need for orthogonal approaches for unbiased identification and analysis of PTrMs. Since
small DNA viruses that replicate in the nucleus have both to employ cellular machinery to transcribe and translate
their gene products, and also develop ways to counteract host defenses, these viruses harness and manipulate
cellular RNA processing pathways. Virus infections thus provide elegant biological models to decipher how RNA
transcription and its chemical modifications can be regulated and exploited to direct the host cell machinery
towards production of viral progeny. Based on preliminary data generated by our collaborative team, our
objectives in this proposal are to employ Adenovirus as a model system to study PTrMs on non-coding and
messenger viral RNAs and how they are exploited to counter host defenses and promote efficient viral RNA
processing and progeny production. Adenoviruses are large non-eveloped viruses and include over 50 distinct
strains which elicit a wide range of effects in humans, from respiratory infections to life-threatening organ
problems in people with weakened immune systems. Adenoviruses hijack the host cell machinery to express
viral genes, and this is achieved by overtaking RNA-mediated processes. Our preliminary data show how
Adenovirus infection exploits the m6A modification on RNA to promote splicing and also alters RNA-protein
interactions. Here we will develop improved mass spectrometry (MS) technologies to quantitatively and
comprehensively detect RNA modifications and RNA-protein interactions over a detailed time-course of infection.
Our MS technology will be paired with cellular and genetic assays to determine how the modifications are utilized
by Adenovirus to promote growth and counter host defenses in ways that culminate in human disease. These
high-throughput unbiased MS-based technologies and approaches will be broadly applicable to enable new
biology in virus-host interactions and epitranscriptomics.

## Key facts

- **NIH application ID:** 10825547
- **Project number:** 5R01AI118891-10
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Benjamin A Garcia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $580,123
- **Award type:** 5
- **Project period:** 2015-04-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825547

## Citation

> US National Institutes of Health, RePORTER application 10825547, Viral modulation of epitranscriptomic mechanisms (5R01AI118891-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10825547. Licensed CC0.

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