There are over 170 types of chemical modifications discovered across all the RNA categories in living organisms, which constitute the epitranscriptome. Emerging as an additional mechanism of post-transcriptional regulation of genetic information, these RNA modifications and the epitranscriptome have been tightly associated with the RNA fate and various human diseases. Among these distinct RNA modifications, m⁶A is the most prevalent and involved in coordinating many aspects of biological activities. It has been known that the deposition and removal of the m⁶A modification are dynamic and reversible processes in cells and regulated by different groups of enzymes and proteins, including the m⁶A writers, erasers and readers. The m⁶A writers include the methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14) and Wilms’ tumor 1-associating protein (WTAP), which are responsible for adding the methyl group to N6 position on adenosine to generate the m⁶A modification, and the fat-mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5) have been identified as the enzymes to remove it. The YTH family and heterogenous nuclear ribonucleoproteins (HNRNPs) as well as the eukaryotic initiation factor (eIF) and insulin like growth factor 2 (IGF2) are discovered to be the endogenous proteins to recognize the m⁶A modification and mediate its biological functions. Dissecting the precise roles of m⁶A in biological or disease processes has been complicated by the fact that the m⁶A's function is position, transcript, cell and tissue contextdependent. Conventional genetic methods manipulating m⁶A writers and erasers not only lead to the global change of m⁶A levels across the whole transcriptome but also lack temporal controls. Without proper research tools, the relationship between m⁶A and the phenotypic outcomes within particular RNA and cellular contexts remains elusive.