# Systematic approaches to deciphering cis regulation of A-to-I RNA editing

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $417,979

## Abstract

Given that there are much fewer genes in metazoans than previously predicted, there are
several mechanisms in biology to generate diversity at the transcriptional and translational
level. One such mechanism is RNA editing, in which a base in RNA is modified by an enzyme
to form a different base. The most common type of RNA editing is Adenosine-to-Inosine (A-
to-I), catalyzed by the adenosine deaminase acting on RNA (ADAR) family of enzymes. ADAR
binds to double-stranded RNA and de-aminates Adenosine to form Inosine, which is then
read as Guanosine by the cellular machinery. Thus, RNA editing can contribute to the
diversity of the transcriptome by changing the amino acid sequences of proteins, altering the
locations of start or stop codons, influencing alternative splicing patterns, and affecting the
ability of miRNAs to bind to their target sites. Tight regulation by RNA editing plays import
roles as exemplified by a number of cases linked to diseases. Our recent results suggest that
cis regulation plays a major role in RNA editing regulation. However, how RNA editing is
regulated by cis regulatory elements remains largely unexplored. There is a lack of systematic,
genome-wide studies to elucidate the cis regulation of RNA editing. In this work, we aim to
develop systematic approaches to deciphering the regulatory code of RNA editing cis
regulation. First, we will map cis quantitative trait loci (QTLs) that are associated with RNA
editing levels across human individuals. Second, we will examine editing QTLs also involved
in other cellular processes that may be functionally related to RNA editing. Third, we will
apply synthetic biology approaches to introduce mutations in the dsRNA substrates to
measure editing specificity and efficiency for variants at each base in vitro and in human
cells, and experimentally determine ADAR binding affinity and RNA secondary structure in
vitro. Taken together, the goals of this proposed project will provide an unprecedented
understanding of primary sequence and secondary structure features that govern the cis
regulation of A-to-I RNA editing, and reveal the functional relationship between RNA editing
and other cellular processes.

## Key facts

- **NIH application ID:** 10000212
- **Project number:** 5R01GM124215-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jin Billy Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,979
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000212

## Citation

> US National Institutes of Health, RePORTER application 10000212, Systematic approaches to deciphering cis regulation of A-to-I RNA editing (5R01GM124215-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10000212. Licensed CC0.

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