# Post-transcriptional regulation of cell plasticity

> **NIH NIH R35** · EMORY UNIVERSITY · 2024 · $111,243

## Abstract

SUMMARY
Cell plasticity is the ability of cells to change their phenotypes without genetic mutations in response to
environmental cues. This cellular behavior is crucial for the development and progress of complex diseases,
such as immune responses and cancer. Changes in cellular transcription programs have long been considered
a major factor in defining the fate of cells during cell-type switching. However, the role that post-transcriptional
mechanisms can play in regulating cell fate, specifically in response to rapid changes in the environmental cues,
is a black box. A long-term goal of my laboratory is to identify the post-transcriptional mechanisms that regulate
protein synthesis and understand their contribution to cellular plasticity. Here, we focus on two areas of post-
transcriptional gene regulation: mRNA modifications and translational control. While there has been impressive
progress towards understanding the role of RNA modifications and translational regulation in controlling cellular
homeostasis, there is a significant gap in our knowledge of how these processes can rapidly affect cellular
plasticity in response to the changes in environmental cues. The eukaryotic initiation factor 3 (eIF3) has emerged
as a master player in translation regulation by promoting or suppressing the translation of a subset of mRNAs.
However, how this key initiation factor controls cell plasticity is a mystery. Our data indicate that eIF3 is critically
important for morphological transition in the yeast Candida albicans. In Theme 1, we will address the role of eIF3
in controlling cell plasticity in C. albicans by answering two key questions: 1) What are the composition and the
interactome of eIF3 in different cell types of C. albicans? and 2) What is the role of C. albicans eIF3 in regulating
mRNA translation during the yeast-to-hyphae transition? Our second area of research (Theme 2) is focused on
understanding how RNA modifications regulate cell plasticity in C. albicans. Our work demonstrates that mRNAs
are differentially methylated in different cell types in C. albicans, and inhibiting the mRNA methylation impairs
cell plasticity in this organism. By combining novel genetic tools and reagents that we have recently developed
with biochemical assays, proteomics, and next-generation sequencing we will answer two key questions: 3)
What is the mechanism of m6A deposition in mRNA during cell-type switching in C. albicans? and 4) How do
m6A mRNA modifications contribute to cell-type switching in C. albicans? Our findings will provide significant
insights into the mechanisms of post-transcriptional control of cell plasticity at the mRNA or translation level and
will aid in understanding how dysregulation of these processes contributes to human disease.

## Key facts

- **NIH application ID:** 11037302
- **Project number:** 3R35GM150760-02S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Sohail Khoshnevis
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $111,243
- **Award type:** 3
- **Project period:** 2023-07-21 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037302

## Citation

> US National Institutes of Health, RePORTER application 11037302, Post-transcriptional regulation of cell plasticity (3R35GM150760-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11037302. Licensed CC0.

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