# Regulation and Function of RNA Editing in Human Transcriptomes

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $361,200

## Abstract

PROJECT SUMMARY
The central objective of this research is to comprehensively investigate the variation, regulation, and
functional consequences of RNA editing in human transcriptomes. RNA editing has emerged as an
important and widespread mechanism for generating transcriptome diversity in eukaryotic cells. Aberrant
RNA editing has been implicated in a variety of diseases including neurological diseases and cancer.
The most abundant type of RNA editing is the A-to-I RNA editing (the deamination of adenosine to
inosine) mediated by the ADAR family of RNA editing enzymes. High-throughput RNA sequencing
studies have revealed millions of A-to-I RNA editing sites in the human transcriptome. Despite the
explosion in the number of identified RNA editing sites, there remain significant knowledge gaps about
the regulation and function of RNA editing. The landscapes of RNA editing can be dynamically regulated
among different tissues or cell types or in response to stimuli, as well as become dysregulated in
diseases. While previous studies on the regulation of RNA editing mainly focused on the ADAR enzymes,
the roles of other trans-acting regulators such as RNA binding proteins have largely been unexplored.
Moreover, the functions of most A-to-I RNA editing events are currently unknown. Previous functional
studies have investigated RNA editing events in coding regions of selected genes. Recent data indicate
that the vast majority of A-to-I RNA editing events occur in non-coding regions, such as 5'-UTR, intron,
and 3'-UTR, suggesting widespread regulatory effects of editing on the RNA. Indeed, RNA editing may
influence a variety of regulatory processes at the post-transcriptional level, such as the regulation of RNA
splicing, localization, stability, and translational efficiency. Of note, work from us and others has shown
that RNA editing can create or disrupt functional microRNA target sites in the 3'-UTR, suggesting that
RNA editing can directly regulate mRNA translation or stability. In three complementary and tightly
integrated research aims, we will investigate the regulation of RNA editing by trans-acting regulators and
environmental stimuli (Aim 1), the genetic variation and
phenotypic association
of RNA editing in human
populations (Aim 2), and the functional consequences of RNA editing on mRNA translation and stability
(Aim 3). Collectively, the proposed studies will provide significant insights into the regulation, genetic
variation, and function of RNA editing. Additionally, through this project we will develop innovative
approaches for quantitative analyses of RNA editing using a variety of transcriptome sequencing
technologies. We anticipate that these approaches will be broadly useful for studying RNA editing as well
as other types of RNA variants and modifications in eukaryotic transcriptomes.

## Key facts

- **NIH application ID:** 10236289
- **Project number:** 5R01GM121827-05
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Lan Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $361,200
- **Award type:** 5
- **Project period:** 2017-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236289

## Citation

> US National Institutes of Health, RePORTER application 10236289, Regulation and Function of RNA Editing in Human Transcriptomes (5R01GM121827-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10236289. Licensed CC0.

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