Roles of m⁶A RNA Modification in Normal Development and Disease

During normal developmental and disease processes gene expression plays a central role. Multiple layers of regulation play roles in expression of developmental regulatory genes in a timely manner to maintain the developmental process smoothly and in order. Epitranscriptomic gene expression regulation through post-transcriptional m⁶A RNA modification has emerged as a novel concept of gene expression regulation in recent years. The reversible m⁶A modification which is imprinted in the RNA transcripts by methyltransferases called “writers” and removed by demethylases called “erasers” has been discovered in both protein coding mRNAs and noncoding RNAs. The recognition of this modification mark by RNA-binding proteins called “readers” determines the stability, translation, or translocation of the transcripts carrying the m⁶A modification. By controlling the life cycle of the mRNA transcript of a particular gene m⁶A thus up/downregulates its expression. This mode of gene expression regulation not only is important for normal developmental processes but also plays major roles in disease processes as evidenced by many recently published studies. Abnormal m⁶A levels and aberrant expression of its regulatory proteins have been implicated in multiple disease processes particularly in different types of cancers. In this chapter, we compiled the literatures focusing on the involvement of m⁶A modification in normal development as well as in pathogenesis of diseases. We also highlighted the emerging role of m⁶A modification in diseases caused by environmental exposure to toxic chemical substances.