Novel Insights Into the Multifaceted Functions of RNA n-Methyladenosine Modification in Degenerative Musculoskeletal Diseases.

N-methyladenosine (mA) is an important modification of eukaryotic mRNA. Since the first discovery of the corresponding demethylase and the subsequent identification of mA as a dynamic modification, the function and mechanism of mA in mammalian gene regulation have been extensively investigated. "Writer", "eraser" and "reader" proteins are key proteins involved in the dynamic regulation of mA modifications, through the anchoring, removal, and interpretation of mA modifications, respectively. Remarkably, such dynamic modifications can regulate the progression of many diseases by affecting RNA splicing, translation, export and degradation. Emerging evidence has identified the relationship between mA modifications and degenerative musculoskeletal diseases, such as osteoarthritis, osteoporosis, sarcopenia and degenerative spinal disorders. Here, we have comprehensively summarized the evidence of the pathogenesis of mA modifications in degenerative musculoskeletal diseases. Moreover, the potential molecular mechanisms, regulatory functions and clinical implications of mA modifications are thoroughly discussed. Our review may provide potential prospects for addressing key issues in further studies.