# The Role of mRNA Degradation in Embryonic Cell Fate Specification

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2024 · $36,530

## Abstract

Project Summary
During development, cells undergo dynamic changes in gene expression that are required for appropriate cell
fate specification. Although developmental gene expression is best studied in terms of transcriptional regulation,
the regulation of mRNA degradation may also have important contributions to these expression patterns. Defects
in mRNA decay machinery have been linked to diseases with distinct phenotypes, such as osteosarcoma and
neurodegenerative diseases. In addition, the widespread degradation of maternal mRNAs in all animals during
early embryogenesis is critical for the control of development to switch from maternally provided to zygotically
encoded products. Studies of maternal and zygotic mRNA decay dynamics have established that transcript
stability is largely regulated by the binding of protein or RNA factors to cis-regulatory elements within the 3’
untranslated region (3’ UTR) of transcripts. Codon usage is another major determinant of mRNA stability, as
translation can affect mRNA stability in a codon-dependent manner. Considering the great diversity of RNA-
binding proteins and small RNAs in eukaryotes, along with alternative splicing and polyadenylation, the
regulation of mRNA degradation has the potential to be highly complex. This complexity may shape precise gene
expression patterns during development, though the extent of developmentally regulated zygotic mRNA
degradation is unclear. To explore this, I am studying zygotic mRNA degradation in Caenorhabditis elegans
throughout embryonic development. In Aim 1, I will generate a transcriptome-wide map of mRNA decay rates
throughout embryogenesis with spatial and temporal resolution. Transcript half-lives will be determined using
single cell RNA-sequencing to measure mRNA abundance in embryonic cells treated with a transcription inhibitor.
To validate half-lives measured by this transcription inhibition approach, I will use metabolic labeling and
degradation of RNA polymerase II as two orthogonal methods to measure decay rates. Mechanisms of
differential mRNA degradation, namely genes with different rates of decay in different cell types, will be explored
using a transgene approach. In Aim 2, I will establish the roles of the major 5′ to 3′ and 3′ to 5′ mRNA decay
pathways in development. I will identify mRNA targets of both pathways through RNA-sequencing of staged
embryos depleted of the cognate exoribonuclease. Genes that are significantly upregulated compared to control
embryos will be treated as putative targets. Additionally, I will determine the roles of both pathways in cell fate
specification by analyzing cell fate marker expression in exoribonuclease-depleted embryos using live imaging.
By characterizing mRNA decay rates across cell types and developmental stages and establishing mechanisms
of differential mRNA degradation, I will begin to uncover the role of zygotic mRNA turnover in embryonic cell fate
specification. Such findings will provide a more com...

## Key facts

- **NIH application ID:** 10874387
- **Project number:** 5F31HD107858-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Felicia Peng
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $36,530
- **Award type:** 5
- **Project period:** 2023-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874387

## Citation

> US National Institutes of Health, RePORTER application 10874387, The Role of mRNA Degradation in Embryonic Cell Fate Specification (5F31HD107858-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10874387. Licensed CC0.

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