TITLE:
Molecular Mechanisms of the Interaction between m6A Modification and Endoplasmic Reticulum Stress and Their Regulatory Roles in Disease Progression
AUTHORS:
Sina Yang, Shiyan Gu, Zuoshun He
KEYWORDS:
m6A Modification, Endoplasmic Reticulum Stress, Unfolded Protein Response, Cell Fate, Disease Mechanisms
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.4,
April
8,
2026
ABSTRACT: N6-methyladenosine (m6A), the most prevalent post-transcriptional modification in eukaryotic messenger RNA (mRNA), plays a pivotal role in the regulation of gene expression. Endoplasmic reticulum stress (ERS) serves as a critical defensive mechanism for cells responding to the disruption of internal homeostasis and is intimately associated with the initiation and progression of various major diseases. In recent years, accumulating evidence has revealed a complex bidirectional regulatory network between m6A modification and ERS. On one hand, m6A modification directly modulates the initiation and intensity of ERS by regulating the translation efficiency or mRNA stability of unfolded protein response (UPR)-related genes. On the other hand, ERS signaling exerts feedback regulation on the expression and activity of the m6A methyltransferase machinery (the “writers”, “erasers”, and “readers”), thereby reshaping the cellular transcriptomic landscape. This review summarizes the regulatory mechanisms underlying the interaction between m6A modification and ERS, explores how this dynamic network influences cell fate, and further elaborates on their pathophysiological roles in tumors, neurodegenerative diseases, and metabolic diseases, aiming to provide a theoretical basis and potential strategies for targeted therapies against these diseases.