# Post-Transcriptional Regulation of Gene Expression by Ribosome-Binding Protein 1

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2024 · $754,509

## Abstract

PROJECT SUMMARY/ABSTRACT
Secreted and membrane proteins are important for cell survival and crosstalk. The rough endoplasmic
reticulum (ER) is a dynamic organelle that adjusts to changes in protein folding demand by regulating secretory
protein throughput. While recent studies examined transcriptional regulation of genes encoding secretory
proteins in the heart, post-transcriptional regulation of protein expression remains largely unstudied. Here,
post-transcriptional regulation genes encoding secretory proteins will be studied, which we found to be an
important layer of gene expression control. ER-associated RNA-binding proteins that bind targeting elements
in transcripts may orchestrate post-transcriptional regulation of gene expression at the ER. Our pilot data
identified ribosome-binding protein 1 (RRBP1) as a novel protein that binds RNA at the ER of cardiac
myocytes, which we found to be necessary for secretory protein expression. We demonstrated that RRBP1
increased in cardiac disease settings that affect the ER secretory capacity. We also revealed that RRBP1
expression decreased during postnatal development, coordinate with decline in ER secretory capacity. When
RRBP1 expression was increased in cardiac myocytes, transcripts encoding ER-targeted proteins increased
and cardiac structure and function after myocardial infarction improved. Our concept is that RRBP1 localizes
specific mRNAs that encode secretory proteins to the ER, and that this localization is important for the
synthesis of proteins that improve ER secretory capacity, as well as secreted proteins. This has led to the
hypothesis that RRBP1 mechanistically links post-transcriptional control of secretory protein expression and
ER secretory capacity, which we posit to be adaptive in the heart. This hypothesis will be addressed in three
specific aims: 1) Assess the effects of RRBP1 on mRNA metabolism, 2) Examine the effects of RRBP1 on
secretory protein synthesis and cellular crosstalk, and 3) Determine the protective potential of increasing
RRBP1. These studies will be performed using an innovative molecular strategy for endogenous re-expression
of a gene that is downregulated specifically in cardiac myocytes to mechanistically dissect roles for RRBP1 as
a regulator of gene expression and response to injury. Impact: Coupling this strategy with cardiac myocyte-
specific RNA profiling and ribosome profiling will enable us to determine the effects of RRBP1 on all aspects of
RNA metabolism dynamics in cardiac myocytes, in vivo. These studies will reveal previously unappreciated
roles for RRBP-1 mediated post-transcriptional regulation of ER-localized mRNAs in cardiac myocyte viability
and cardioprotection.

## Key facts

- **NIH application ID:** 10891137
- **Project number:** 1R01HL170223-01A1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Shirin Doroudgar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $754,509
- **Award type:** 1
- **Project period:** 2024-05-10 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891137

## Citation

> US National Institutes of Health, RePORTER application 10891137, Post-Transcriptional Regulation of Gene Expression by Ribosome-Binding Protein 1 (1R01HL170223-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10891137. Licensed CC0.

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