# Investigating the role of m6A RNA methylation during adenovirus infection

> **NIH NIH F32** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $67,446

## Abstract

Project Summary
 The discovery of reversible N6-methyladenosine (m6A) modification of RNA has fundamentally altered
the way we think of the central dogma of molecular biology. M6A is added post-transcriptionally to RNA, where
it has been implicated in such diverse processes as RNA splicing, nuclear export, stability, and translation. The
mechanisms in which post-transcriptional modifications of RNA controls RNA fate has opened up a new field of
biology dubbed “Epitranscriptomics”. Since small DNA viruses that replicate in the nucleus have to employ
cellular machinery to transcribe and translate their gene products, viruses have developed ways to harness
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. Shortly after the discovery of m6A on human RNA in 1974, it was
demonstrated that adenovirus RNAs are also marked by m6A. However, the effect of m6A modifications on
Adenovirus has never been deciphered and in the intervening 40 years no progress has been made in
understanding how epitranscriptomic modifications impact the life cycle of DNA viruses. Adenovirus has served
as an excellent model for illuminating fundamental cellular processes such as RNA capping, splicing, and
polyadenylation, and I propose to use Adenovirus as a model pathogen to discover novel m6A-regulating factors
of mRNA transcripts in human cells.
 My preliminary data map the site specific locations of m6A-modifications within Adenoviral RNA
transcripts. Furthermore, we show that knockdown of the human m6A methyltransferase complex negatively
affects Adenoviral late protein expression and infectious virus production. At the same time, the virus recruits
members of the host m6A pathway to sites of viral replication. The specific aims of this proposal are to 1)
determine host factors that methylate and bind methylated adenoviral RNA transcripts, 2) determine the
function of m6A in the life cycle of adenovirus, and 3) determine the extent that host RNA methylation is
altered during viral infection. In Aim 1 I will investigate the human methyltransferase METTL3 as the possible
source of Adenoviral RNA methylation. In Aim 2 I will explore possible roles for m6A methylation in the adenoviral
life cycle such as RNA splicing and export from the nucleus. In Aim 3 I will define the changing methylation status
of host RNA in response to Adenovirus infection. Together, these experiments will provide insight into how DNA
viruses interact with and control host RNA biogenesis machinery. The completion of these aims, and the training
provided within, will provide the foundation for future investigation on my path to being an independent
investigator.

## Key facts

- **NIH application ID:** 9857470
- **Project number:** 5F32AI138432-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Alexander Matthew Price
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857470

## Citation

> US National Institutes of Health, RePORTER application 9857470, Investigating the role of m6A RNA methylation during adenovirus infection (5F32AI138432-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857470. Licensed CC0.

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