# Regulation of epidermal growth and differentiation through mRNA export

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $433,446

## Abstract

Project Summary/Abstract
Background: Transcriptional mechanisms that regulate epidermal homeostasis have
been well established but recently we have discovered that mRNA export mechanisms
play prominent roles in maintaining epidermal self-renewal. We have shown that RBM15
associates with the NXF1 exporter only in stem and progenitor cells while ZC3H18
associates with NXF1 in differentiated cells. This association allows RBM15 or ZC3H18
to control the mRNA export of key transcripts involved in epidermal growth and
differentiation.
Objective/hypothesis: This proposal seeks to understand the regulation of epidermal
stem and progenitor cell self-renewal and differentiation through post-transcriptional
mechanisms. We have identified RNA binding proteins that are necessary for the export
of self-renewal mRNAs to promote epidermal self-renewal. Similarly we have identified
RNA binding proteins that are necessary to export differentiation inducing mRNAs to
promote epidermal differentiation. Furthermore mutations in these proteins can lead to
clonal expansion of the skin due to altered regulation of epidermal growth and
differentiation.
Specific Aims: (1) To determine the role of RBM15 and ZC3H18 on epidermal growth
and differentiation. (2) To determine the molecular mechanisms of RBM15 and ZC3H18
wildtype and mutant proteins impact on epidermal homeostasis.
Study Design: To study epidermal homeostasis in a more clinically relevant setting, we
generate 3-dimensionally intact human skin, containing human epidermal cells (that
have been permanently knocked down for RBM15 or ZC3H18) in the context of human
dermal stroma and basement membrane, regenerated on immune compromised mice.
By using this model, we can perform loss of function experiments on RBM15 or ZC3H18
in regenerated human skin to characterize their role in epidermal growth and
differentiation. We will also use RNA immunoprecipitations followed by next generation
sequencing to determine the RNAs associated with these proteins.

## Key facts

- **NIH application ID:** 10863998
- **Project number:** 5R01AR081215-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** GEORGE L SEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $433,446
- **Award type:** 5
- **Project period:** 2022-08-02 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10863998

## Citation

> US National Institutes of Health, RePORTER application 10863998, Regulation of epidermal growth and differentiation through mRNA export (5R01AR081215-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10863998. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*