MINI REVIEW article
Front. Genet.
Sec. RNA
This article is part of the Research TopicFunctions of RNA and RNA-Binding Proteins in DiseaseView all 4 articles
Regulatory Roles of the circRNA–RBP Axis in Exercise-Induced Skeletal Muscle Remodeling: Mechanistic Controversies and Translational Illusions
Provisionally accepted
- Harbin Sport University, Harbin, China
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Metabolic health and physical performance rely upon skeletal muscle adaptation that is a result of exercise. Recent advancements in high-throughput sequencing and functional genomics have successfully identified a vast landscape of exercise-responsive circRNAs, providing critical insights into the molecular complexity of muscle adaptation. While these studies have established a foundational framework for understanding the circRNA–RBP axis, there are serious issues related to current research. There are serious issues related to current research: an insufficient level of endogenous circRNA to produce substantial ceRNA effects, unconfirmed circRNA scaffolding due to overactivity of RBPs, poor conservation of so-called exercise-related circRNAs evolutionarily, and the over-interpretation of specific effects. The article focuses on basic concerns of the ceRNA model quantitative limitations, and specificity debate of the scaffolding model, current model and technical gaps, etc. and suggests an experimental framework transitioning from "narrative models" to "physiologically credible mechanisms," offering references for future rigorous research and elucidating the authentic role of the circRNA–RBP axis.
Keywords: circRNA, Competing endogenous RNA, Exercise adaptation, Exosomes, Experimental rigor, Muscle Plasticity, RNA-Binding Proteins, Skeletal muscle remodeling
Received: 21 Dec 2025; Accepted: 12 Feb 2026.
Copyright: © 2026 Liu, Yang, Chen, Liu, Mao and Mi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhujun Mao
Zheng Mi
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