# Prion-based regulation of RNA-modifying enzyme activities

> **NIH NIH R35** · UNIVERSITY OF OREGON · 2022 · $368,750

## Abstract

Project Summary/Abstract
Prion proteins are notorious in biology for causing deadly, infectious brain diseases.
Beyond disease, however, prions completely altered our understanding of heredity, and
contrary to their reputation, they are not only disease-causing agents. Instead, they are
found across kingdoms of life, and are an epigenetic mechanism that affects a panoply
of cellular processes, also producing biologically beneficial traits. In this proposal we
focus on prions that regulate RNA, specifically, prionogenic conformations of RNA-
modifying enzymes. These highly conserved enzymes catalyze numerous chemical
modifications on RNA that are critical for their structure and function. The goal of our
research is to understand how prion-like forms of these enzymes may alter their activities
on RNA, producing changes to gene expression, and ultimately, leading to long-lasting,
heritable growth phenotypes, such as resistance to environmental stress. One recent
such example that we have detailed is a prionogenic form of a pseudouridine synthase,
which affects cell proliferation, aging, and protein synthesis. This work led us to
investigate the capacity for other RNA-modifying enzymes to have prion-like behavior,
and we now have several new examples for study. In this proposal, we will investigate
whether RNA modifications are changed when the enzymes that make them adopt prion-
like conformations, the effects these changes have on gene expression, the role for
enzyme catalysis, the structure of the infectious prion protein, and whether the prion-
based behavior that we have observed in budding yeast is conserved in human cells. We
approach these questions using a combination of genetics, high-throughput sequencing,
classical biochemical methods, and fluorescence microscopy. In summary, this work aims
to uncover the molecular details of epigenetic, prion-based regulation of RNA that affects
cell growth and survival.

## Key facts

- **NIH application ID:** 10453589
- **Project number:** 5R35GM143125-02
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** David M. Garcia
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $368,750
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453589

## Citation

> US National Institutes of Health, RePORTER application 10453589, Prion-based regulation of RNA-modifying enzyme activities (5R35GM143125-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10453589. Licensed CC0.

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