N6-methyladenosine methyltransferases: functions, regulation, and clinical potential

Abstract

N6-methyladenosine (m6A) has emerged as an abundant modification throughout the transcriptome with widespread functions in protein-coding and noncoding RNAs. It affects the fates of modified RNAs, including their stability, splicing, and/or translation, and thus plays important roles in posttranscriptional regulation. To date, m6A methyltransferases have been reported to execute m6A deposition on distinct RNAs by their own or forming different complexes with additional partner proteins. In this review, we summarize the function of these m6A methyltransferases or complexes in regulating the key genes and pathways of cancer biology. We also highlight the progress in the use of m6A methyltransferases in mediating therapy resistance, including chemotherapy, targeted therapy, immunotherapy and radiotherapy. Finally, we discuss the current approaches and clinical potential of m6A methyltransferase-targeting strategies.

The N6-methyladenosine reader protein YTHDC2 promotes gastric cancer progression via enhancing YAP mRNA translation

“…N6-methyladenosine (m 6 A) is the most common internal modification in eukaryotic mRNA [4] . It is dynamically installed and removed, and acts as a new layer of mRNA fate, involving in m 6 A methyltransferase, demethylase and binding protein [5] , [6] , [7] . m 6 A binding protein, known as “reader”, is capable of decoding m 6 A methylation and yielding a series of functional signals, mainly including YTH domain containing protein, IGF2BP and HNRNP families [ 8 , 9 ].…”

m6A Modification Patterns With Distinct Immunity, Metabolism, and Stemness Characteristics in Soft Tissue Sarcoma

“…The key role of m6A modification mediated regulators in modulating DNA repair and genome stability has gradually attracted attention (38). Some m6A methyltransferases can modify and regulate the levels of RNAs involved in DNA damage and repair, which in turn affect genomic instability (39). For example, the m6A methyltransferase METTL3 is activated by ATMmediated phosphorylation and localized to DNA damage sites, where it promotes HRD repair (40).…”

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

“…N6-methyladenosine (m6A) is one of the most common internal transcription modifications in eukaryotic messenger RNA (mRNA) ( Huang et al, 2021 ; Oerum et al, 2021 ). The molecule was first identified in the 1970s, but recent studies have shown that m6A-associated mutations are closely related to BC occurrence ( Liu et al, 2021b ).…”