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Network-based modelling reveals cell-type enriched patterns of non-coding RNA regulation during human skeletal muscle
Jonathan C Mcleod1, Changhyun Lim1,2, Tanner Stokes1
1Department of Kinesiology, McMaster University, Hamilton, Ontario, L8S 4L8, Canada.
NAR Molecular Medicine
|December 13, 2024
Summary
Researchers identified 110 non-protein-coding RNAs (ncRNAs) linked to human skeletal muscle growth during resistance training. These ncRNAs interact through various pathways and cell types, revealing new insights into muscle hypertrophy.
Area of Science:
- Molecular Biology
- Genomics
- Human Physiology
Background:
- Non-protein-coding RNAs (ncRNAs) play crucial roles in development and disease.
- Studying ncRNAs in human skeletal muscle presents challenges with traditional short-read sequencing.
Purpose of the Study:
- To investigate cell-type specific ncRNA responses during muscle growth at scale using a customized RNA pipeline and network modeling.
- To identify novel ncRNAs associated with muscle hypertrophy in humans.
Main Methods:
- Utilized a customized RNA pipeline and network modeling for transcriptome-wide profiling.
- Analyzed data from five human resistance-training studies (n=144 subjects).
- Employed advanced bioinformatics to identify and characterize ncRNAs linked to muscle growth.
Main Results:
- Identified 110 ncRNAs associated with muscle growth in vivo, with 61% of subjects showing muscle mass accrual.
- Confirmed known hypertrophy-related ncRNAs like CYTOR and discovered novel ones: PPP1CB-DT, EEF1A1P24, and TMSB4XP8.
- Demonstrated that hypertrophy-linked ncRNA genes operate through multiple cell types and interacting pathways, with MYREM showing specific myonuclear expression.
Conclusions:
- Single-cell-associated ncRNAs can be identified from bulk muscle transcriptomic data.
- Hypertrophy-linked ncRNAs mediate muscle growth effects via diverse cell types and functional pathways.
