# Mitochondrial RNA defense pathways in the oocyte

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $418,200

## Abstract

Abstract
Maternal aging has dramatic effects on the oocyte quality and competence, and it is well known that
mitochondrial function plays important roles in oocyte health. Post-transcriptional gene regulation within the
oocyte is also essential for its normal development and function. In somatic cells, mitochondria are key
effectors of post-transcriptional gene regulation, where RNA sensors located on the mitochondria react in
response to double stranded RNA (dsRNA) to invoke the mitochondrial RNA defense pathway. The role of the
mitochondrial defense pathway, which includes RNA-editing and RNA sensing is unknown in the oocyte, even
though the oocyte has an abundance of dsRNA within it. Here we provide preliminary data demonstrating an
abundance of RNA edits in mouse and human oocytes, the expression of `adenosine deaminase acting on
RNA' (ADAR), as well as downstream components of the RNA sensing pathway in mouse and human oocytes.
Most importantly, we show that inhibition of ADAR RNA editing in oocytes results in increased accumulation of
reactive oxygen species (ROS), thus implicating RNA editing as a regulator of mitochondrial function and
possibly oocyte quality. Lastly, data from reproductively old mice indicate that the genes involved in RNA
editing (ADAR1) and RNA sensing (p32) are decreased in oocytes, thus potentially leading to aberrant
activation of mitochondrial RNA-dependent defense pathway. We propose that oocyte mitochondria are key
effectors of the RNA editing and RNA sensing mechanisms within oocytes, under conditions such as aging,
hyper-activity of mitochondrial RNA defense may increase ROS accumulation and ultimately impact oocyte
quality. The central hypothesis we intend to test in this proposal is that the mitochondrial RNA defense
pathway is a critical regulator of oocyte competence/quality. To test the central hypothesis, Specific Aim 1
will identify the specific oocyte RNA edits occurring in three species of mammalian oocytes. Specific Aim 2 will
determine the role of ADAR1 and RIG-I/MAVS in the regulation of mitochondrial function in oocytes using
state-of-the-art mitochondrial functional assays and assess the impact on oocyte quality/developmental
potential. Specific Aim 3 will examine how advanced reproductive age impacts mitochondrial RNA sensing
pathways in both mouse and human oocytes. Ultimately, this work may provide a mechanistic link (dsRNA
defense pathway) that can explain the known mitochondrial dysfunction associated with oocytes from
reproductively old mice and older IVF patients.

## Key facts

- **NIH application ID:** 9878896
- **Project number:** 5R01HD094545-03
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** LANE K. CHRISTENSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $418,200
- **Award type:** 5
- **Project period:** 2018-04-25 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878896

## Citation

> US National Institutes of Health, RePORTER application 9878896, Mitochondrial RNA defense pathways in the oocyte (5R01HD094545-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878896. Licensed CC0.

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