# Deciphering The Role of RNA Modifications In Maternal Mrna Clearance

> **NIH GM R35** · OLD DOMINION UNIVERSITY · 2026 · $440,000

## Abstract

Abstract
Maternal RNA clearance is an essential process that occurs in the absence of transcription in all sexually
reproducing species examined. Stored maternal transcripts sustain early embryonic development prior to
activation of the embryonic genome. Perturbations of maternal mRNA degradation can either halt or irreparably
alter the maternal-to-zygotic transition, leading to early embryonic demise. Oocytes are unique cells in which
translation and RNA clearance are coupled, in the absence of new transcription. Maternal mRNA is eliminated
via translationally coupled mRNA degradation, a process that includes recruitment of mRNA to the ribosome,
shortening of the poly(A) tail, decapping, and degradation by both 5′ and 3′ exonucleases. Mechanisms that
regulate translationally coupled mRNA degradation are poorly understood. Recent studies have established
RNA modifications as regulators of maternal mRNA clearance. Our previous work established that inosine
RNA modifications within the coding region of mRNA can impact maternal mRNA stability through a translation
mechanism. Here, I describe two research directions I will pursue in the next 5 years that address fundamental
questions about the role of RNA modifications in maternal mRNA clearance. The first direction will investigate
the relationship between inosine mRNA modifications in translation. The second direction will focus on
identifying the relationship between inosine RNA modifications and other RNA modifications, and how this
combined “RNA modification code” can regulate RNA stability and translation during maternal mRNA
clearance. We will use innovative molecular analyses, novel RNA-sequencing approaches, proteomics, in vivo
imaging, and combined single molecular/single oocyte assays to test how inosine impacts translation, alters
the occurrence of amino acid substitutions, and how this facilitates maternal mRNA clearance. In addition, I will
catalog the “RNA modification code” on whole, individual transcrip

## Key facts

- **NIH application ID:** 11386351
- **Project number:** 5R35GM159853-02
- **Recipient organization:** OLD DOMINION UNIVERSITY
- **Principal Investigator:** Pavla  Brachova
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $440,000
- **Award type:** 5
- **Project period:** 2025-08-15T00:00:00 → 2030-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11386351

## Citation

> US National Institutes of Health, RePORTER application 11386351, Deciphering The Role of RNA Modifications In Maternal Mrna Clearance (5R35GM159853-02). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/11386351. Licensed CC0.

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