# Transcriptome processing networks in skeletal muscle: mechanisms and functions

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $453,413

## Abstract

Project Summary
The long-term goal of this project is to determine the extent, regulatory mechanisms, and functional
consequences of regulated pre-mRNA processing in skeletal muscle. A large number of genes express pre-
mRNAs that undergo alternative splicing to produce conserved muscle-specific protein isoforms the functions
of which are unknown. These isoforms often appear during late fetal or early postnatal development. Disruption
of alternative splicing is a common feature of diseases affecting skeletal muscle, often involving reversion to
fetal isoforms, yet little is known about the contributions of these changes to pathogenesis. An underlying
hypothesis of this proposal is that a focus on genes with conserved fetal and adult protein isoforms, including
adult isoforms that are muscle-specific, will discover not only previously unknown isoform-specific functions but
also previously unknown gene functions critical for adult muscle homeostasis. To identify the functions of
alternative splicing events in vivo we are using CRISPR-mediated removal of exons that undergo muscle-
specific and/or postnatally regulated inclusion. In the first aim, we will determine the functions of a striated
muscle-specific isoform of the Map4 microtubule-binding protein in which deletion of the muscle-specific exon
significantly disrupts microtubule architecture in skeletal muscle myofibers and impacts muscle force
generation. In the second aim we will determine the function of the skeletal muscle-specific Limch1 isoform,
the absence of which also decreases skeletal muscle function in vivo. In the third aim we will use CRISPR-
mediated introduction of epitope tags into endogenous genes to monitor the temporal and spatial details of the
alternative splicing transitions and adult muscle-specific isoforms at the level of individual cells in vivo. This
study is expected to identify previously unknown gene functions, increase understanding of adult skeletal
muscle homeostasis and the impact of its disruption in disease.

## Key facts

- **NIH application ID:** 9889041
- **Project number:** 5R01AR060733-07
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Thomas A Cooper
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $453,413
- **Award type:** 5
- **Project period:** 2011-04-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889041

## Citation

> US National Institutes of Health, RePORTER application 9889041, Transcriptome processing networks in skeletal muscle: mechanisms and functions (5R01AR060733-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9889041. Licensed CC0.

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