Novel insights into the METTL3-METTL14 complex in musculoskeletal diseases

N6-methyladenosine (m(6)A) modification, catalyzed by methyltransferase complexes (MTCs), plays many roles in multifaceted biological activities. As the most important subunit of MTCs, the METTL3-METTL14 complex is reported to be the initial factor that catalyzes the methylation of adenosines. Recently, accumulating evidence has indicated that the METTL3-METTL14 complex plays a key role in musculoskeletal diseases in an m(6)A-dependent or -independent manner. Although the functions of m(6)A modifications in a variety of musculoskeletal diseases have been widely recognized, the critical role of the METTL3-METTL14 complex in certain musculoskeletal disorders, such as osteoporosis, osteoarthritis, rheumatoid arthritis and osteosarcoma, has not been systematically revealed. In the current review, the structure, mechanisms and functions of the METTL3-METTL14 complex and the mechanisms and functions of its downstream pathways in the aforementioned musculoskeletal diseases are categorized and summarized.

Automated summary

N6-methyladenosine (m(6)A) modification, catalyzed by methyltransferase complexes (MTCs), plays important roles in diverse biological activities. The METTL3-METTL14 complex, as the most crucial subunit of MTCs, has been reported as the initial factor for adenosine methylation. Recent evidence suggests that the METTL3-METTL14 complex plays a pivotal role in musculoskeletal diseases in an m(6)A-dependent or -independent manner. However, the specific roles of the METTL3-METTL14 complex in certain musculoskeletal disorders, including osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma, remain to be systematically revealed. This review categorizes and summarizes the structure, mechanisms, and functions of the METTL3-METTL14 complex, as well as the mechanisms and functions of its downstream pathways in the aforementioned musculoskeletal diseases.