# SnoRNA-guided modifications of mRNA

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $322,000

## Abstract

ABSTRACT
Recent studies have demonstrated that post-transcriptional mRNA modifications can regulate gene expression,
with implications for cellular differentiation, development, and cancer. For example, the m6A modification can
regulate fundamental aspects of mRNA biology, such as splicing, stability, and translation. In contrast, much less
is known about internal 2'-O-methylation (Nm) on mRNA. Now, using genetic models, our data suggest that small
nucleolar RNAs (snoRNAs) can guide internal Nm modification of mRNA, via the enzyme fibrillarin (FBL). Our
findings also suggest that Nm modification can regulate mRNA levels and protein expression in vivo. In this
application, we propose to define the mechanisms that lead to Nm modification of mRNA, and to understand
how Nm regulates gene expression. Our long-term goals are to determine how snoRNA-guided modifications of
mRNA impact gene expression, cell biology, and organism health. The objective of this proposal is to specifically
determine how snoRNA-guided Nm modification regulates the expression of Pxdn mRNA. Our central hypothesis
is that Rpl13a snoRNAs guide FBL-mediated Nm modification of Pxdn mRNA, and that the modification
increases mRNA abundance but inhibits protein translation. We propose to test our hypothesis with the following
Specific Aims: (1) Define the snoRNA(s) and protein components that target Pxdn mRNA for Nm modification;
(2) Define how snoRNA-guided modification of Pxdn regulates RNA and protein expression; and (3) Discover
the network of snoRNA-guided Nm modifications in cells. Successful completion of these Aims will define, for
the first time, how Nm modification of mRNA regulates gene expression. We also expect that our work will define
a new role for snoRNAs in the modification of mRNA. As such, this work will open new avenues in the study of
both RNA modifications and snoRNA biology.

## Key facts

- **NIH application ID:** 10307575
- **Project number:** 5R01GM135383-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Christopher Lee Holley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $322,000
- **Award type:** 5
- **Project period:** 2019-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10307575

## Citation

> US National Institutes of Health, RePORTER application 10307575, SnoRNA-guided modifications of mRNA (5R01GM135383-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10307575. Licensed CC0.

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