# Molecular mechanisms that regulate ADAR target recognition and RNA editing in vivo

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $36,663

## Abstract

Project Summary
Sequence alterations that change the genome-encoded information present in RNAs, referred to as RNA
editing, provide a powerful way to diversify the transcripts expressed in an organism’s tissues over time. The
objective of the parent research proposal is to determine molecular mechanisms of how RNA binding proteins
influence substrate recognition by the ADAR RNA editing enzymes. ADARs catalyze millions of adenosine (A)
to inosine (I) modifications in eukaryotic transcriptomes to play an essential role in the creation of proteomic
and phenotypic diversity. Despite the prevalence of A-to-I editing, there is a gap in knowledge of how ADARs
edit specific adenosines to varying degrees during development and in specific cell types. My lab has made
significant contributions to this outstanding question by identifying roles for naturally occurring editing-deficient
ADAR proteins in regulating editing. The proposed research takes an integrated approach using both the
model organism, Caenorhabditis elegans, and human glioblastoma (brain tumor) cell lines with a combination
of biochemistry, genomics, and molecular biology to connect the molecular mechanisms of RNA recognition by
ADARs to functional consequences on RNA editing and gene expression. Our main goals are to define the
molecular mechanism of how an editing-deficient ADAR protein can recruit the RNA editing enzyme to specific
adenosines in vivo, dissect the mechanism of how certain neural transcripts are selectively edited and to
determine the cellular targets and impact of the editing-deficient human ortholog on the glioblastoma
transcriptome.
 An essential approach used in our work is the generation and biochemical/genomic analysis of
transgenic C. elegans. This is a powerful system as loss of ADARs results in behavior/neuronal phenotypes in
C. elegans in contrast to lethality in mice. Therefore, we can mechanistically dissect the process of ADAR
editing at specific sites by using genetic mutants in both the RNA editing enzyme and the editing-deficient
ADAR protein. In addition, using fluorescent proteins fused to ADAR substrates, we can determine molecular
features critical for editing of specific adenosines in vivo. In this supplemental proposal, I am requesting funds
for the replacement of my aging fluorescence microscope that is used to both prepare our transgenic worms
for experiments and screen the creation of additional transgenic strains for the proposed research. While this
instrument has served us well and is still used, the repairs needed, and age of the system have indicated that it
is near the end of its lifetime. The purchase of a Zeiss Discovery V20 fluorescence dissecting microscope will
enable us to perform the proposed research, and the dedicated use of this instrument by my laboratory will
increase experimental output to meet the goals of determining the molecular mechanisms that regulate RNA
editing in vivo.

## Key facts

- **NIH application ID:** 10581855
- **Project number:** 3R01GM130759-03S1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Heather Ann Hundley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $36,663
- **Award type:** 3
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10581855

## Citation

> US National Institutes of Health, RePORTER application 10581855, Molecular mechanisms that regulate ADAR target recognition and RNA editing in vivo (3R01GM130759-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10581855. Licensed CC0.

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