# Analysis of the Role of Post-Transcriptional Regulation by the Poly(C) Binding Proteins in Pancreatic Beta Cell Homeostasis

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $32,610

## Abstract

Project Summary
β cell dysfunction and β cell failure play central roles in the pathogenesis of Type 2 Diabetes Mellitus (T2DM).
Increasing evidence has suggested that post-transcriptional regulation of gene expression is essential for β cell
function and survival. However, the underlying mechanisms governing how the post-transcriptional landscape
is shaped to promote β homeostasis remains largely unexplored. A growing body of evidence has implicated
RNA binding proteins (RBPs) in influencing the metabolism of mRNAs that encode products essential for β cell
survival. Despite these findings, few RBPs have been examined in understanding how the post-transcriptional
milieu is shaped to maintain β cell homeostasis. Based on a Translating Ribosomal Affinity Purification (TRAP)
screen in our laboratory using the Min6 β cell line, the poly(C) binding protein family of RNA binding proteins,
specifically PCBP1 and PCBP1, have been raised as potential post-transcriptional regulators of β cell identity
and survival genes. Thus, the goal of this proposal is to elucidate the mechanistic and physiological importance
of post-transcriptional regulation by PCBP1 and PCBP2 in β cells. In the first aim of this proposal, the in vivo
roles exerted by PCBP1 and PCBP2 will be examined by crossing mice harboring conditional alleles for Pcbp1
and Pcbp2 with a β cell specific Cre deleter strain. Morphological and functional analyses will be performed
with β cells that have individual and combined Pcbp1/2 deficiency. Further, the inclusion of a lineage trace
allele will allow us to determine the fate of Pcbp1/2 deficient β cells. The second part of this proposal will
examine how glucose shapes the post-transcriptional landscape of β cells. β cells are highly regulated by
glucose to allow for tight regulation of blood glucose homeostasis. Interestingly, preliminary demonstrate that
Pcbp2 expression substantially increases in murine and human islets exposed to high glucose, pointing to a
role in PCBP2 post-transcriptionally mediating the effects of glucose in the β cell. To determine the influence of
glucose on the post-transcriptional landscape and the role of PCBP2 in this response, TRAP will be used in
wild-type and Pcbp2-deficient β cells exposed to low and high glucose. TRAP has the distinct advantage of
determining ribosomal occupancy, or translational efficiency, specifically in β cells within isolated pancreatic
islets, which are a heterogenous tissue type. At the same time, analysis of total RNA from isolated β cells will
reveal to what extent PCBP2 impacts other aspects of post-transcriptional gene regulation affected by elevated
glucose. Additionally, Cross-Linking and Immunoprecipitation Sequencing (CLIP-Seq) will be performed in
wild-type and Pcbp2-deficient β cells to identify PCBP2 binding sites transcriptome-wide to determine whether
PCBP2 binds to transcripts it functionally impacts. Altogether, these experiments will establish a paradigm for
PCBP1 and PCBP2...

## Key facts

- **NIH application ID:** 10020171
- **Project number:** 5F31DK117577-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Matthew Haemmerle
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,610
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020171

## Citation

> US National Institutes of Health, RePORTER application 10020171, Analysis of the Role of Post-Transcriptional Regulation by the Poly(C) Binding Proteins in Pancreatic Beta Cell Homeostasis (5F31DK117577-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10020171. Licensed CC0.

---

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