# A-to-I RNA modifications in mouse oocytes

> **NIH NIH R00** · OLD DOMINION UNIVERSITY · 2024 · $87,651

## Abstract

PROJECT SUMMARY/ABSTRACT
The primary objective of this proposal is to facilitate the development of Dr. Brachova into an independent
research scientist. This objective will be accomplished through a combination of active mentorship, didactic
training, enrichment activities, and research. The mentorship phase is well described by her mentors and
includes weekly contact and formal course work. The core of the research focuses on the role of a post-
transcriptional regulation mechanism known as RNA editing in overall oocyte quality. Defects in oocyte growth
and meiotic maturation represent a significant cause of human birth defects, miscarriage, and infertility. The
contribution of RNA post-transcriptional modifications is emerging as an important regulator of RNA stability
and oocyte quality, however the role of adenosine deaminase acting on double stranded RNA (ADAR1), which
catalyzes the deamination of an adenosine (A) into inosine (I) remains unexplored. The goal of this research
is to determine the effect of ADAR1 RNA editing on RNA stability and oocyte competence in young and
old mice. Preliminary data show that ADARFL/FLZP3-Cre oocytes have reduced embryonic developmental
potential, suggesting that ADAR1 is a novel factor that contributes to female fertility. We also show that
oocytes and eggs from aged individuals have reduced RNA editing efficiency, suggesting that RNA editing
deficiencies could be involved in female age-associated decline of fertility. The central hypothesis is that
ADAR1 RNA editing is a novel mechanism for maintaining female fertility through the regulation of RNA
stability during oocyte growth and early embryonic development. The hypothesis will be tested in two
independent specific aims. Specific Aim 1 will assess the role of ADAR1 A-to-I RNA editing in the regulation of
maternal mRNA dosage in the oocyte and early embryo. Specific Aim 2 will determine how ADAR1 A-to-I RNA
editing effects mRNA degradation in oocytes. The proposed research will utilize oocytes and eggs from young
and maternally aged mice to explore the role of A-to-I editing in oogenesis and age-related reduction in fertility.
This proposal represents an innovative approach to study oocyte competence, and has the potential to expand
our understanding of female fertility. Furthermore, the studies proposed herein are integral to enhance the
scientific training of Dr. Brachova and enable her to accomplish her goal of achieving independence and
becoming an independent scientist in the field of female reproduction.

## Key facts

- **NIH application ID:** 11178183
- **Project number:** 6R00HD099269-06
- **Recipient organization:** OLD DOMINION UNIVERSITY
- **Principal Investigator:** Pavla Brachova
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $87,651
- **Award type:** 6
- **Project period:** 2019-08-26 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11178183

## Citation

> US National Institutes of Health, RePORTER application 11178183, A-to-I RNA modifications in mouse oocytes (6R00HD099269-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11178183. Licensed CC0.

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