# Base-resolution mapping and site-specific epitranscriptomic studies in the brain

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2021 · $469,882

## Abstract

PROJECT SUMMARY
Both neurodevelopment and the synaptic plasticity events that underlie learning and memory
rely heavily on tightly regulated gene expression programs and rapid, finely-tuned translation of
messenger RNA (mRNA) transcripts. The degradation, stability, and translation of mRNA has, in
recent years, been found to be regulated by adenosine methylation, which alters both transcript
structure and the recruitment of RNA-binding proteins that inform these activities. Recent
identification of and experimentation with the methyltransferases (“writers”), demethylases
(“erasers”), and specific methyladenosine binding proteins (“readers”) have established that
these epitranscriptomic mRNA regulatory processes are both dynamic and tightly regulated.
Although the most well-studied of these modifications is N6-methyladenosine (m6A), N1-
methyladenosine (m1A) has also recently emerged as a prevalent epitranscriptomic mark.
Current methods used to explore these modifications require large sample sizes and are
inherently low-resolution. These limitations preclude them from mapping and quantifying the
epitranscriptome in specific brain regions, or in clinical biospecimens. Here, we describe
preliminary development of innovative technologies to precisely sequence and probe the
function of specific m6A and m1A modifications. We propose to leverage these foundations in
the service of the following specific aims: 1) Evolve and establish high-resolution, antibody-free
m6A and m1A mapping platforms for brain analysis, 2) Design and validate a molecular toolkit to
manipulate transcript-specific m6A and m1A modifications in vivo, and 3) Catalog m6A and m1A
modifications in the brain across development, neuron populations, activity state, and in
synapses, and determine their function in relation to learning and memory. Our findings will
illuminate how the epitranscriptomic landscape and specific mRNA transcripts in discrete
neuronal populations regulates gene expression to inform complex neuronal processes, such as
development, learning and memory, and how perturbations thereof result in abnormal brain
function such as learning impairment. Importantly, this translational, functional validation of our
new tools, which will be made available to the research community, provides a strong
foundation for their usage to specifically interrogate how mRNA modifications are perturbed in
other pathological contexts.

## Key facts

- **NIH application ID:** 10225604
- **Project number:** 5R01MH122142-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Bryan Dickinson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $469,882
- **Award type:** 5
- **Project period:** 2019-09-25 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225604

## Citation

> US National Institutes of Health, RePORTER application 10225604, Base-resolution mapping and site-specific epitranscriptomic studies in the brain (5R01MH122142-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225604. Licensed CC0.

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