# Transcriptome-wide base-resolution sequencing of pseudouridine in human normal and AD brain tissues-CEGS Admin supplement 2020-2021

> **NIH NIH RM1** · UNIVERSITY OF CHICAGO · 2020 · $397,500

## Abstract

Abstract
Transcriptome-wide base-resolution sequencing of pseudouridine in human normal and
AD brain tissues
Studies in the past several decades have revealed several layers of complex biological
regulations through various RNA species. Among these, arguably the most complicated and
recently emerging one involves diverse chemical modifications on almost all RNA species. Over
170 types of different post-transcriptional RNA modifications are known to exist in all kingdoms of
life. Research in the past 8-9 years revealed prevalent chemical modifications on messenger RNA
and regulatory non-coding RNAs. These modifications, in particular those in mammalian systems,
can be dynamic and reversible, and can dramatically impact a broad range of biological processes.
For example, about 0.4-0.6% of all adenosines in mammalian mRNA are N6-methyladenosine
(m6A) modified, corresponding to on average ~3 m6A residues per mRNA molecule. Lack of m6A
methylation is lethal in mammals; animal model studies have shown that RNA m6A methylation is
essential or critical to almost all stem cell differentiation processes in most tissue types examined
so far.
Pseudouridine (Ψ), with a ~0.2% of Ψ/U ratio in most mammalian mRNA, is the second most
abundant mammalian mRNA modification. Its abundance is approximately 1/3 of that of m6A, or
one Ψ per mRNA molecule on average in mammals, and roughly 5-10 folds higher than the
abundances of other mammalian mRNA modifications. There are 13 annotated potential
pseudouridine synthases in the human genome, and mutations of some of these enzymes can
lead to neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. Due to a
lack of highly sensitive and quantitative sequencing methods previously, we lacked both
understanding of the substrates of these pseudouridine synthases and the comprehensive map
of Ψ in mammals, which will help us understand its characteristics and functions.
We propose to apply a newly developed sequencing method from our CEGS (Center for dynamic
RNA epitranscriptome) and sequence Ψ at base-resolution in normal and AD human brain tissues.
This effort will generate the first reference pseudouridine epitranscriptome in human brain tissues
and will examine alternations in human AD tissues. AD fly models will be employed to determine
the contribution of epitranscriptome alterations to AD pathogenesis. Enabled by the new
technologies developed in our CEGS, this supplement application represents the first study on
this important topic.

## Key facts

- **NIH application ID:** 10123724
- **Project number:** 3RM1HG008935-05S2
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** CHUAN HE
- **Activity code:** RM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,500
- **Award type:** 3
- **Project period:** 2016-09-27 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123724

## Citation

> US National Institutes of Health, RePORTER application 10123724, Transcriptome-wide base-resolution sequencing of pseudouridine in human normal and AD brain tissues-CEGS Admin supplement 2020-2021 (3RM1HG008935-05S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10123724. Licensed CC0.

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