# ADAR-editing landscape dysregulation in neuropsychiatric disorders

> **NIH NIH F31** · KENT STATE UNIVERSITY · 2021 · $26,655

## Abstract

Project Abstract:
 Adenosine deaminase acting on RNA (ADAR) editing plays a major role in shaping transcriptome
diversity by creating variant isoforms that enable fine-tuning of calcium-mediated excitatory and other signaling
needed for brain development, neural plasticity and mood regulation. The spatio-temporal ADAR editing
landscapes are tightly regulated by controlling ADAR expression levels to preserve preferential binding and
editing. Previous studies have shown that activation of the interferon pathways of the innate immune system –
such as those seen in viral infections - leads to increased expression of ADAR1p150, which ultimately results
in changes to ADAR editing patterns. Furthermore, common side effects to innate immune activation by
interferon alpha therapies include increased risk of depression and suicide. The changes in spatio-temporal
regulation of editing patterns can lead to a wide spectrum of neurological symptoms, including neuropsychiatric
disorders (e.g., decreased ADAR editing in the serotonin receptor subunit2C in the prefrontal cortex observed
in individuals who commit suicide). Yet, our understanding of ADAR editing landscapes remain cursory.
Advances in high throughput RNA-seq enable more accurate variant calling from the sequencing reads,
providing a way to map ADAR editing patterns in the transcriptome. However, there are no computational
pipelines focused on ADAR editing that are easy to use, are reproducible and can handle large scale analysis.
I have recently built a pipeline to handle meta-analysis of RNA-seq data that incorporates variant calling steps,
but further work is needed to validate this tool to assure accuracy and reproducibility of results. It can then be
used to map the spatio-temporal variation of ADAR editing landscapes. The proposed project will study ADAR
editing landscapes in the following ways: (i) new computational pipelines will be benchmarked to use variant
calling with RNA-seq datasets using simulated reads, (ii) ADAR editing landscape diversity in the publicly
available human samples will be mapped; the computational predictions and hypotheses generated from the
pipeline will be validated using (iii) measuring calcium flux in cells with known differential ADAR editing
landscapes caused by PolyI:C (viral infection mimic) treatment. The proposed work will yield a validated
pipeline capable of mapping ADAR editing landscapes with machine learning algorithms. Defining ADAR
editing landscapes is paramount to biomarker discovery and can influence precision medicine applications in
diagnosis and treatment of neuropsychiatric disorders. This project will allow for me to gain the knowledge
base necessary to become an independent researcher with a unique skill set of both computational and
benchwork methods to advance the field of neuroscience.

## Key facts

- **NIH application ID:** 10238770
- **Project number:** 5F31MH123131-02
- **Recipient organization:** KENT STATE UNIVERSITY
- **Principal Investigator:** Noel-Marie Plonski
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $26,655
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-07-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238770

## Citation

> US National Institutes of Health, RePORTER application 10238770, ADAR-editing landscape dysregulation in neuropsychiatric disorders (5F31MH123131-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10238770. Licensed CC0.

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