Structural Insights into N⁶-methyladenosine (m⁶A) Modification in the Transcriptome

More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N⁶-methyladenosine (m⁶A), have been detected in mRNA, opening the window into the realm of epitranscriptomics. The m⁶A modification is the most abundant modification in mRNA and non-coding RNA (ncRNA). At the molecular level, m⁶A affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA (miRNA) maturation, playing essential roles in a range of cellular processes. The m⁶A modification is regulated by three classes of proteins generally referred to as the "writer" (adenosine methyltransferase), "eraser" (m⁶A demethylating enzyme), and "reader" (m⁶A-binding protein). The m⁶A modification is reversibly installed and removed by writers and erasers, respectively. Readers, which are members of the YT521-B homology (YTH) family proteins, selectively bind to RNA and affect its fate in an m⁶A-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the m⁶A modification, and provide our insights into the m⁶A-mediated gene regulation.