# Systematic approaches to deciphering regulation and function of RNA editing in brain

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $667,294

## Abstract

Project Summary
Recent advances in sequencing technologies and bioinformatic methodologies have enabled
great progress in better understanding RNA processing, regulation and modification. RNA
editing is a prevalent type of RNA modification where the RNA sequences are altered through
insertion, deletion or substitution of nucleotides. In mammals, the most common type of RNA
editing is adenosine to inosine (A-to-I) editing. A-to-I editing is essential for normal life and
development. A handful of A-to-I editing sites have been discovered with critical roles in
neuronal signaling, by modulating membrane excitability, neurotransmission plasticity and signal
transduction. In addition, aberrant RNA editing has been implicated in human neuropsychiatric
diseases, such as Autism, Alzheimer’s disease, depression, schizophrenia, and amyotrophic
lateral sclerosis. While numerous RNA editing sites have been identified via RNA-sequencing
(RNA-seq) and related technologies, major challenges exist in understanding the function and
regulation of RNA editing. The vast majority of known human RNA editing sites reside in non-
coding regions, such as introns and untranslated regions, that may confer regulatory function to
the related gene, especially at the level of post-transcriptional regulation. Therefore, there is a
great demand for in-depth studies of the functional impacts of RNA editing on post-
transcriptional regulation. The regulatory mechanisms of RNA editing are poorly characterized.
Except the ADAR enzymes, few proteins and their mechanisms of action have been examined
for RNA editing. A major challenge is the lack of efficient and systematic methods to pinpoint
novel regulators. In this project, we propose to extend our recent success at developing
bioinformatic and experimental frameworks to address the above challenges. We will capitalize
on the large collection of RNA-seq data sets derived from postmortem brain samples. We will
develop and apply novel methodologies to make full use of these data sets, complemented by
further bioinformatic prediction and high-throughput experimental testing, to predict and validate
the molecular function of RNA editing and related regulatory mechanisms. This work will allow a
previously unattained level of understanding of the molecular basis of RNA editing and provide
new insights to the involvement of RNA editing in human biology.

## Key facts

- **NIH application ID:** 10734760
- **Project number:** 5R01MH123177-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Xinshu Grace Xiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $667,294
- **Award type:** 5
- **Project period:** 2020-12-01 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10734760

## Citation

> US National Institutes of Health, RePORTER application 10734760, Systematic approaches to deciphering regulation and function of RNA editing in brain (5R01MH123177-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10734760. Licensed CC0.

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