# ALTERNATIVE SPLICING REGULATION AND MEMBRANE TRAFFICKING

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $320,991

## Abstract

ABSTRACT / SUMMARY
The complexity of organisms does not correlate with the number of protein encoding genes. Regulatory
mechanisms have contributed to the diversification of gene function during evolution. Alternative splicing is a
posttranscriptional mechanism that explains how single genes can produce more than one transcript due to the
inclusion or exclusion of specific regions. In humans, more than 90% of genes undergo alternative splicing,
consistent with the increased cellular and functional complexity of higher eukaryotes. Genome wide studies have
exponentially increased the number of splicing isoforms and networks with completely unknown functions. Genes
encoding membrane trafficking proteins are developmentally regulated by alternative splicing specifically in
striated muscles between birth and adulthood. This finding raises the question of the physiological implications
of this level of regulation. Understanding the role of splicing regulation in the expression and function of proteins
involved in trafficking and membrane dynamics is the knowledge gap inspiring our project.
 The scientific premise of this R01 proposal is that alternative splicing regulation of trafficking proteins
plays key developmental roles in cells, tissues, and organs. The fundamental question asked in this proposal
is how alternative splicing controls membrane trafficking in specific tissues and cell types. We will tackle this
question in two aims: (aim 1) what are the regulatory mechanisms that coordinate these splicing transitions?
(aim 2) what are the functional consequences of splicing regulation of membrane trafficking genes?
 In Specific Aim 1, we will identify the role of two RNA-binding proteins (PTBP and QK) and epigenetics
in splicing regulation of membrane trafficking genes in muscle cell differentiation. In Specific Aim 2, we will
determine the downstream functional consequences of alternative splicing regulation of the membrane trafficking
gene Trip10 (Cdc42 interacting protein-4, CIP4) utilizing cell culture experiments and animal studies. Overall,
after completion of this project we will have identified the molecular mechanisms involved in alternative splicing
regulation of membrane trafficking proteins, and their physiological significance.

## Key facts

- **NIH application ID:** 10360604
- **Project number:** 5R01GM130866-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jimena Giudice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $320,991
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360604

## Citation

> US National Institutes of Health, RePORTER application 10360604, ALTERNATIVE SPLICING REGULATION AND MEMBRANE TRAFFICKING (5R01GM130866-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10360604. Licensed CC0.

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