# Regulatory roles of the epitranscriptome and RNA structurome during vertebrate development

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2023 · $54,664

## Abstract

PROJECT SUMMARY/ABSTRACT (as submitted in original application)
In all animals, the maternal-to-zygotic transition allows the transfer of information required for a single zygote to
develop into a mature organism. After fertilization, the maternal program, composed of maternally-inherited
mRNAs and proteins, drives cellular development and is replaced by the zygotic program. Because this transition
occurs primarily in a transcriptionally silent embryo, it relies heavily on post-transcriptional regulation. Failure to
properly regulate maternally-inherited mRNAs generally leads to developmental arrest or abnormalities. Recent
studies have shown that maternal mRNAs are decorated with RNA modifications, collectively known as the
‘epitranscriptome’, that correlate with different mRNA fates. Moreover, we and others performed global analyses
of mRNA structure dynamics during the maternal-to-zygotic transition and identified numerous regions that are
structurally remodeled during this fundamental process, many of which impact mRNA decay. These studies
suggest that RNA modifications and dynamic RNA structures are emerging as key regulators of gene expression
during the maternal-to-zygotic transition. However, the detailed landscape of the epitranscriptome and dynamic
RNA structures, and their roles in gene regulation during the maternal-to-zygotic transition remain poorly
understood. Furthermore, RNA modifications and structures affect one another to regulate RNA functions, but
little is known about how they interact to control gene expression during vertebrate development. The primary
goal of my lab is to understand how the epitranscriptome and RNA structures mediate gene regulatory networks,
separately and cooperatively, during vertebrate development and how their dysfunction promotes developmental
defects or diseases. Here, we hypothesize that RNA modifications and structures interact with trans-factors to
participate in the post-transcriptional regulatory landscape driving vertebrate development. To test this
hypothesis, we will combine zebrafish —an in vivo model of vertebrate development— and its genetic toolbox
with innovative multi-omics approaches. Over the next five years, we will inspect the native transcriptome to
generate global, yet detailed, maps of the epitranscriptome during the maternal-to-zygotic transition, and study
how specific RNA modifications impact gene expression. We will also decipher the RNA folds formed by dynamic
regions of the transcriptome and analyze their effect on RNA regulation. We will identify trans-factors interacting
with RNA modifications and structures of interest and study the consequences of their loss-of-function on gene
expression and vertebrate development. Finally, we will examine how RNA modifications and structures
cooperate to modulate post-transcriptional regulation. Successful completion of these investigations will greatly
increase the existing knowledge of how RNA modifications and structures orchest...

## Key facts

- **NIH application ID:** 10797217
- **Project number:** 3R35GM146883-01S1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Jean-Denis Beaudoin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $54,664
- **Award type:** 3
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797217

## Citation

> US National Institutes of Health, RePORTER application 10797217, Regulatory roles of the epitranscriptome and RNA structurome during vertebrate development (3R35GM146883-01S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10797217. Licensed CC0.

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