The Proteins of mRNA Modification: Writers, Readers, and Erasers

Over the past decade, mRNA modifications have emerged as important regulators of gene expression control in cells. Fueled in large part by the development of tools for detecting RNA modifications transcriptome wide, researchers have uncovered a diverse epitranscriptome that serves as an additional layer of gene regulation beyond simple RNA sequence. Here, we review the proteins that write, read, and erase these marks, with a particular focus on the most abundant internal modification, N⁶-methyladenosine (m⁶A). We first describe the discovery of the key enzymes that deposit and remove m⁶A and other modifications and discuss how our understanding of these proteins has shaped our views of modification dynamics. We then review current models for the function of m⁶A reader proteins and how our knowledge of these proteins has evolved. Finally, we highlight important future directions for the field and discuss key questions that remain unanswered.