# RNA Regulation in the Pancreatic Beta Cell

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2020 · $36,210

## Abstract

Project Summary
Establishing and maintaining a robust population of functional hormone-secreting endocrine cells is critical for
regulating blood glucose homeostasis, which remains a challenge for individuals with Type 1 and Type 2
diabetes. Traditionally, endocrine cells have been molecularly defined by their gene expression patterns;
however, recent studies have revealed the previously unappreciated importance of co- and post-transcriptional
RNA regulation, such as modification, localization, alternative splicing and transcript stability, in the specification
and function of differentiated cells. Regulation of RNAs is emerging as a critical player in establishing and
maintaining a robust population of functional hormone-secreting endocrine cells. RNA regulation, including
splicing and stability, are coordinated by RNA-binding proteins (RBPs). Each RBP can have hundreds of targets
within a cell, making their potential impact on cellular identity and function extensive. Recent studies have shown
dysregulation of RBPs and aberrant mRNA splicing activity in islets of diabetic patients compared to healthy
controls. Additionally, my preliminary data provides some of the first evidence that β cell function requires specific
RBPs. Furthermore, our lab has shown differential splicing of over 1,000 genes between endocrine cell types
and my own analysis of cytokine treated human β cells as a model of autoimmune destruction revealed 2,250
dysregulated splicing events, including an RBP, Rbfox2. Together these data point toward a previously
unappreciated role for RBPs in endocrine cells and offers a new perspective to examine β cell function. In this
proposal I have outlined the evidence for the extensive impact of Rbfox2 regulation of β cell function. Rbfox2 is
enriched in endocrine cells of pancreatic islets and has a highly conserved RNA binding sequence making it an
ideal candidate to evaluate RBP mediated RNA regulation in the β cell. Conditional loss of Rbfox2 in the pancreas
results in impaired blood glucose regulation without a significant change in islet cell numbers or morphology,
suggesting that islet function is disrupted. Additionally, loss of Rbfox2 in β cells results in aberrant splicing and/or
differential expression of critical β cell specific genes, including MafA. By furthering our understanding of the role
of RBPs and alternative splicing in diabetes, this project provides a unique perspective on a complex disease
and will ultimately push the boundaries of therapeutic treatments of diabetes. The experiments proposed will not
only uncover how β cell function is finetuned at the level of RNA but could potentially describe novel function for
the Rbfox2 in regulating transcript stability.

## Key facts

- **NIH application ID:** 10143967
- **Project number:** 1F31DK126320-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Nicole D Moss
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $36,210
- **Award type:** 1
- **Project period:** 2020-09-04 → 2023-09-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143967

## Citation

> US National Institutes of Health, RePORTER application 10143967, RNA Regulation in the Pancreatic Beta Cell (1F31DK126320-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10143967. Licensed CC0.

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