Reciprocal regulation of m6A RNA methylation and protein post-translational modifications: implications for disease pathogenesis and therapy.

N6-methyladenosine (m6A) is a prevalent epitranscriptional modification in RNA that is crucial for RNA metabolism and biogenesis. Accumulating evidence reveals a complex interplay between m6A and protein post-translational modifications (PTMs)-covalent additions of chemical groups or structural alterations to nascent proteins during or after biosynthesis. This crosstalk involves in disease development and drug response by altering protein properties and functions. However, comprehensive discussion about the roles and mechanisms of m6A and PTMs crosstalk is limited. Here, we present an up-to-date review of this emerging and complex interplay in disease and therapeutic response. We first summarize the crosstalk between m6A and PTMs such as ubiquitination, lactylation, acetylation, phosphorylation, and methylation, organizing our discussion around the three major regulatory factors m6A writers, erasers, and readers. Next, we explore the mechanism of m6A-PTMs crosstalk involved in the pathogenesis and development of diseases, including various cancers, metabolic disorders, and inflammatory diseases. Moreover, we discuss the role of m6A-PTMs crosstalk in drug response, focusing on chemotherapy drugs. In summary, this review provides a framework for understanding the regulatory networks of m6A-PTMs crosstalk in disease pathogenesis, development, and therapeutic response, highlighting potential treatment strategies based on this interplay and suggesting future research directions.