Novel Insights Into the Multifaceted Functions of RNA n6-Methyladenosine Modification in Degenerative Musculoskeletal Diseases

Abstract

N⁶-methyladenosine (m⁶A) is an important modification of eukaryotic mRNA. Since the first discovery of the corresponding demethylase and the subsequent identification of m⁶A as a dynamic modification, the function and mechanism of m⁶A in mammalian gene regulation have been extensively investigated. "Writer", "eraser" and "reader" proteins are key proteins involved in the dynamic regulation of m⁶A modifications, through the anchoring, removal, and interpretation of m⁶A 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 m⁶A 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 m⁶A modifications in degenerative musculoskeletal diseases. Moreover, the potential molecular mechanisms, regulatory functions and clinical implications of m⁶A modifications are thoroughly discussed. Our review may provide potential prospects for addressing key issues in further studies.

Keywords: N6-methyladenosine; degenerative musculoskeletal diseases; degenerative spinal disorders; osteoarthritis; osteoporosis; sarcopenia.