Exercise modulation of the alternative splicing landscape in human tissues

Area of Science:

• Molecular Biology
• Exercise Physiology
• Genomics

Background:

• Exercise elicits multi-organ molecular responses contributing to diverse health benefits.
• Alternative RNA splicing (AS) is crucial for generating transcriptome and proteome diversity.

Purpose of the Study:

• To investigate the temporal effects of acute endurance and resistance exercise on the AS landscape in human skeletal muscle, adipose tissue, and blood.
• To explore regulatory mechanisms of AS changes through integrated multi-omic analyses.

Main Methods:

• Profiling of alternative RNA splicing events in response to acute exercise.
• Integrated multi-omic analyses including RNA sequencing and potentially other omics data.
• Identification and characterization of differential AS (DAS) events and associated regulatory proteins.

Main Results:

• Identified 5102 distinct differential AS (DAS) events, with 89% affecting protein-coding sequences and 67% independent of altered RNA expression.
• Endurance and resistance exercise induced distinct AS alteration patterns with unique temporal dynamics.
• In skeletal muscle, DAS genes were enriched for muscle structure and RNA splicing processes, with splicing machinery components showing multi-level regulation.

Conclusions:

• Alternative RNA splicing regulation is a significant mediator of molecular responses to both endurance and resistance exercise.
• Exercise-induced AS changes contribute to proteome diversity and may underlie some health benefits of physical activity.
• Skeletal muscle exhibits a prominent role in AS regulation following exercise, with coordinated multi-level control of splicing machinery.