Aug 2026· Naunyn-Schmiedeberg's Archives of Pharmacology· 1 citation· 126 references
Medicine
TL;DR
The composition and function of the m6A modification system is summarized, with a focus on its critical roles in skeletal muscle physiology, including satellite cell fate determination, myofiber differentiation and fusion, and energy homeostasis, and the molecular mechanisms by which m6A network dysregulation contributes to skeletal muscle diseases.
N6‐methyladenosine (m6A) is the most abundant internal chemical modification of eukaryotic RNA and a central mechanism of epitranscriptomic gene regulation. Although m6A was first characterized in messenger RNA (mRNA), it is also deposited on ribosomal RNA (rRNA), circular RNA, and other RNA species, where it regulates RNA stability, decay, splicing, nuclear export, translational efficiency, and ribosome function. m6A‐mediated gene regulation has attracted increasing attention as a mechanism that contributes to development, differentiation, metabolism, and disease. Its relevance is also becoming evident in skeletal biology and bone metabolism. METTL3‐mediated m6A modification of mRNA regulates the balance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells and contributes to the maintenance of bone mass, while METTL5‐mediated m6A modification of 18S rRNA supports bone formation through OSER1‐dependent antioxidant regulation. m6A modification has also been implicated in osteoclast differentiation and bone‐resorbing activity, acting through mRNA decay, nuclear export, and transcription factor regulation. In this review, we summarize the basic concepts of m6A modification and discuss its emerging roles in the regulation of bone metabolism, with particular focus on osteoblasts, osteoclasts, osteocytes, and bone marrow mesenchymal stem cells. We also consider the implications of m6A‐mediated epitranscriptomic regulation for oral and skeletal biology.
S. Kokabu, Yuan Quan· Oral Science International· 0 citations
This review focuses on the interplay between immunity and epitranscriptomics and explores the direct and indirect effects of m6A modification on T cells and highlights the pivotal role of m6A regulation in T cell biology and its potential to optimize next-generation immunotherapies.
Yumna A. Butt, Nordin D. Zandhuis, I. Foskolou· Immuno· 0 citations
Skeletal muscle is a core component of the motor system, responsible for movement, posture maintenance, and energy metabolism. It plays a vital role in physiological stress, injury repair, and metabolic homeostasis. In recent years, with the advancement of epigenetic research, RNA modification has become a hot topic in skeletal muscle biology. This article systematically reviews the progress in the study of RNA modification in regulating the fate of skeletal muscle, focusing on the dynamic regulatory mechanisms and pathophysiological significance of N6-methyladenosine (m6A) modification in muscle differentiation, regeneration, and atrophy. It also briefly introduces the existing evidence for 5-methylcytidine (m5C), adenosine-to-inosine (A-to-I) editing, and pseudouridine (Ψ) in skeletal muscle. A comprehensive understanding of these mechanisms is crucial for elucidating the physiological regulation of skeletal muscle and the pathogenesis of related diseases and also provides a new direction for the development of intervention strategies.
Du-Jun Chen, Mailin Gan, Yuhang Lei et al.· Molecules· 0 citations
Breast cancer remains a leading cause of cancer-related mortality worldwide, largely due to its molecular heterogeneity and therapeutic resistance. N6-methyladenosine (m6A) RNA modification has recently emerged as a critical epitranscriptomic regulator involved in diverse aspects of RNA metabolism, including stability, splicing, translation, and degradation. Accumulating evidence suggests that dysregulation of m6A modification is associated with breast cancer progression, metastasis, and treatment resistance. In this review, we systematically summarize the functional roles of m6A regulators, including writers, erasers, and readers, in breast cancer biology. We further discuss the involvement of m6A modification in key oncogenic signaling pathways, metabolic reprogramming, and tumor immune microenvironment remodeling. Importantly, we highlight the emerging clinical potential of m6A regulators as diagnostic and prognostic biomarkers, as well as therapeutic targets for overcoming drug resistance. Finally, we outline current challenges and future perspectives, emphasizing the need for integrating multi-omics approaches and developing m6A-targeted therapies to advance precision oncology in breast cancer.
Zilong Chen, Chi Zhou, Zhuo-Run Song et al.· Cancer Treatment and Researc...· 0 citations
Ferroptosis, an iron-dependent form of regulated cell death, is increasingly recognized as a context-dependent therapeutic vulnerability in cancer, particularly as malignant cells adapt to oxidative, metabolic, and therapy-induced stresses. As a prevalent and reversible epitranscriptomic modification, RNA N6-methyladenosine (m6A) modification orchestrates RNA stability, translation, splicing and decay; consequently, its dysregulation contributes to cancer progression and therapeutic resistance. The intersection of m6A regulation and ferroptosis is therefore biologically important because many ferroptosis threshold genes are short-lived, stress-responsive transcripts controlled by writers, erasers, readers and RNA-binding proteins. This review synthesizes empirical evidence elucidating how m6A regulators remodel cystine import, GPX4-dependent antioxidant defense, FSP1 signaling, lipid metabolism, iron handling, autophagy and tumor-microenvironmental communication. We organize the evidence by regulatory layer rather than cancer type, covering writer-mediated deposition, reader and RNA-binding protein recognition, eraser-dependent demethylation, non-coding RNA and exosomal regulation, and downstream ferroptosis modules. We further discuss how this axis contributes to radiotherapy, chemotherapy, targeted-therapy resistance and ferroptosis-sensitizing combinations. Although m6A-ferroptosis crosstalk offers promising biomarker and therapeutic opportunities, translation requires transcript-level validation, standardized ferroptosis assays, tumor-selective delivery and clinically meaningful patient stratification. A deeper and more precise integration of epitranscriptomics with ferroptosis biology holds the potential to transform stress-adaptive RNA circuits into actionable vulnerabilities for precision cancer therapy.
Qing-Miao Shi, Yang-Ni Li, Chao Guan· Frontiers in Cell and Develo...· 0 citations
N6-methyladenosine (m6A) is a prevalent epitranscriptional modification in RNA that is crucial for RNA metabolism and biogenesis. Accumulating evidence reveals a complex interplay between m6A and protein post-translational modifications (PTMs)-covalent additions of chemical groups or structural alterations to nascent proteins during or after biosynthesis. This crosstalk involves in disease development and drug response by altering protein properties and functions. Nevertheless, comprehensive discussion about the roles and mechanisms of m6A and PTMs crosstalk is limited. Here, we present an up-to-date review of this emerging and complex interplay in disease and therapeutic response. We first summarize the crosstalk between m6A and PTMs such as ubiquitination, lactylation, acetylation, phosphorylation, and methylation, organizing our discussion around the three major regulatory factors m6A writers, erasers, and readers. Next, we explore the mechanism of m6A-PTMs crosstalk involved in the pathogenesis and development of diseases, including various cancers, metabolic disorders, and inflammatory diseases. Moreover, we discuss the role of m6A-PTMs crosstalk in drug response, focusing on chemotherapy drugs. In summary, this review provides a framework for understanding the regulatory networks of m6A-PTMs crosstalk in disease pathogenesis, development, and therapeutic response, highlighting potential treatment strategies based on this interplay and suggesting future research directions.
Xinyi Li, Li-Ting Yang, Xian-Min Zhou et al.· Biochimica et Biophysica Act...· 0 citations
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