Reversible N6-methyladenosine of RNA: The regulatory mechanisms on gene expression and implications in physiology and pathology

Abstract

N6-methyladenosine (m6A) is the most abundant inner RNA modification in eukaryotes. Due to the development of RNA sequencing technology, the distribution pattern of m6A in the transcriptome has been uncovered. Dynamically, the reversible N6-methylation is mediated by two types of proteins, which are classified as “writers” and “erasers”. Under the association of specific co-factors, writers show spatiotemporal N6-methyltransferase activity. Mechanically, m6A can be recognized by “reader” proteins or can directly modify RNA conformation, and it widely affects gene expression by mediating RNA stability, translation, splicing and export. m6A is involved in a series of physiology processes. Dysregulation of m6A is gradually defined as the pathogenesis of some diseases, e.g., cancer and cardiovascular disease. Therefore, a good understanding of m6A is essential for molecular biology and pathology research. In this article we systemically present an overview of the functions and mechanisms of identified m6A regulators. The discovered biological and pathological processes affected by m6A are also summarized. We hope that readers with related research interests benefit from our review.