Structure and function of reader proteins that recognize methylated RNA residues

Recent years have seen significant advances in our understanding of the importance of RNA methylation as an essential mechanism of post-transcriptional regulation of gene expression. RNA methylation is a reversible process relying on the traditional classes of epigenetic 'writer', 'eraser', and 'reader' proteins to install, remove, and recognize methylated residues. While general RNA binding proteins have been extensively studied, proteins that function as readers to specifically recognize methylated RNA and promote functional effects are less explored. In this review, we provide a comprehensive analysis of reader protein structures, highlighting the specific RNA sequence(s) each reader protein targets, critical domains and interactions, and key binding residues/regions. In addition, we discuss the biological outcomes of reader protein binding, specifically within the context of human malignancy. Finally, we provide an update on the current state of small molecule inhibitors of RNA methylation readers. This review underscores the readers' critical role in normal and aberrant cellular signaling while offering valuable insights for the rational design of drugs and probes targeting RNA methylation readers.