Coordinated Regulation of Myonuclear DNA Methylation, mRNA, and miRNA Levels Associates With the Metabolic Response to Rapid Synergist Ablation-Induced Skeletal Muscle Hypertrophy in Female Mice

Authors

Ahmed Ismaeel, University of Kentucky
Nicholas T. Thomas, University of Kentucky
Mariah McCashland, University of Nebraska - Lincoln
Sebastian Edman, Karolinska Institute
Johanna T. Lanner, Karolinska Institute
Vandré C. Figueiredo, Oakland University
Christopher S. Fry, University of Kentucky
John J. McCarthy, University of Kentucky
Yuan Wen, University of Kentucky
Kevin A. Murach, University of Arkansas, FayettevilleFollow
Ferdinand von Walden, Karolinska Institute

Document Type

Article

Publication Date

11-2023

Keywords

RNA sequencing; small RNA sequencing; RRBS; mitochondrial respiration; oxidative metabolism; epigenetics

Abstract

The central dogma of molecular biology dictates the general flow of molecular information from DNA that leads to a functional cellular outcome. In skeletal muscle fibers, the extent to which global myonuclear transcriptional alterations, accounting for epigenetic and post-transcriptional influences, contribute to an adaptive stress response is not clearly defined. In this investigation, we leveraged an integrated analysis of the myonucleus-specific DNA methylome and transcriptome, as well as myonuclear small RNA profiling to molecularly define the early phase of skeletal muscle fiber hypertrophy. The analysis of myonucleus-specific mature microRNA and other small RNA species provides new directions for exploring muscle adaptation and complemented the methylation and transcriptional information. Our integrated multi-omics interrogation revealed a coordinated myonuclear molecular landscape during muscle loading that coincides with an acute and rapid reduction of oxidative metabolism. This response may favor a biosynthesis-oriented metabolic program that supports rapid hypertrophic growth.

Comments

© The Author(s) 2023. Published by Oxford University Press on behalf of American Physiological Society.

Citation

Ismaeel, A., Thomas, N. T., McCashland, M., Edman, S., Lanner, J. T., Figueiredo, V. C., Fry, C. S., McCarthy, J. J., Wen, Y., Murach, K. A., & Walden, F. v. (2023). Coordinated Regulation of Myonuclear DNA Methylation, mRNA, and miRNA Levels Associates With the Metabolic Response to Rapid Synergist Ablation-Induced Skeletal Muscle Hypertrophy in Female Mice. Function, 5 (1), zqad062. https://doi.org/10.1093/function/zqad062

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