# Elucidating the neural specific functions of the RNA-binding protein Caper in neural development and neurodegeneration

> **NIH NIH R15** · UNIVERSITY OF COLORADO · 2022 · $438,000

## Abstract

Project Summary/Abstract
Post-transcriptional gene regulation is a fundamental mechanism that helps regulate the development and
healthy aging of the nervous system. Mutations that disrupt the function of RNA-binding proteins (RBPs), which
regulate post-transcriptional gene regulation, have increasingly been implicated in neurological disorders
including amyotrophic lateral sclerosis, Fragile X Syndrome, and spinal muscular atrophy. Interestingly,
although the majority of RBPs are expressed widely within diverse tissue types, the nervous system is often
particularly sensitive to their dysfunction. The long-term goal of this project is to begin to elucidate how
aberrant RNA regulation that results from the dysfunction of ubiquitously expressed RBPs, leads to tissue
specific pathologies that underlie neurological diseases. To this end, the highly conserved splicing factor Caper
will be used as a model. Caper is widely expressed throughout development and is required for the
development of Drosophila sensory and motor neurons. Furthermore, caper dysfunction causes
neurodegeneration and results in adult locomotor deficits. Though little is known about the function of the
human caper ortholog, RBM39, it is expressed within the nervous system suggesting its neural functions may
be conserved. The research proposed within this application will test the hypothesis that Caper regulates RNA
targets in a combinatorial manner within neuronal cells by participating in specific ribonucleoprotein complexes
(RNPs) within the nervous system. We have identified proteins encoding RBPs that interact with Caper only
within the brain, along with neural specific Caper target RNAs. Using the highly tractable model, Drosophila,
tissue specific molecular genetic manipulations will be used in conjunction with biochemistry to determine the
extent to which Caper functions combinatorially with these RBPs to direct neurogenesis and protect the aging
brain from neurodegeneration. Furthermore, we will further characterize the neurodegenerative phenotypes
associated with caper dysfunction to determine which cell types are undergoing cell death in the aging brain.
Since aberrant RNA regulation has emerged as a common theme in various neurodegenerative and
neurodevelopmental disorders, the knowledge gained from this study has broad implications for understanding
and treating neurological disorders.

## Key facts

- **NIH application ID:** 10577059
- **Project number:** 2R15NS104976-02
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Eugenia C Olesnicky
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $438,000
- **Award type:** 2
- **Project period:** 2018-07-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10577059

## Citation

> US National Institutes of Health, RePORTER application 10577059, Elucidating the neural specific functions of the RNA-binding protein Caper in neural development and neurodegeneration (2R15NS104976-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10577059. Licensed CC0.

---

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