# Gammaherpesviruses induce transfer RNA cleavage

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2024 · $233,250

## Abstract

Project Summary/Abstract
Host transfer RNAs are cleaved into fragments during infection by diverse bacteria and viruses, yet what
triggers this molecular event and how tRNA fragments (tRFs) impact infection remain poorly understood. This
proposal leverages powerful molecular, genetic, and biochemical approaches during gammaherpesvirus
infection to profile differential tRNA cleavage and to assess how tRNA cleavage and/or the resulting tRFs
regulate the antiviral response. The overall objective in this proposal is to profile tRFs in infected primary cells
and define whether tRNA cleavage or tRFs modulate gammaherpesvirus infection. This work explores the
central hypothesis that tRNAs are cleaved in response to viral sensing and that gene regulatory functions of
tRFs further establish an antiviral state. To test this hypothesis, Aim 1 employs a highly innovative sequencing
strategy to accurately sequence tRNAs and their derivatives induced by gammaherpesvirus infection in
primary, immune-competent cells. This aim will identify abundant, and likely functionally relevant, infection-
induced tRFs, as well as introduce a sequencing tool with broad applicability to the tRF field. Aim 2 tests the
hypothesis that tRF biogenesis is part of the host antiviral response by assessing gammaherpesvirus
replication in response to decreased or increased expression of tRFs or tRNA endonucleases. These
experiments will result in fundamental knowledge explaining why tRFs are generated in response to diverse
viruses and reveal broad potential for tRNA-based antiviral therapeutic strategies. The work proposed here is
significant, as it will pioneer the concept of antiviral tRFs, introduce a widely applicable sequencing strategy,
and will ultimately reveal novel tRNA-centric nodes of gene expression control that can be manipulated to
prevent and treat infectious disease.

## Key facts

- **NIH application ID:** 10809442
- **Project number:** 1R21AI173703-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Jessica Mitchell Tucker
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $233,250
- **Award type:** 1
- **Project period:** 2024-06-21 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809442

## Citation

> US National Institutes of Health, RePORTER application 10809442, Gammaherpesviruses induce transfer RNA cleavage (1R21AI173703-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10809442. Licensed CC0.

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