Why does the m6A writer complex require so many proteins?

Abstract

The conversion of adenosine to N6-methyladenosine (m6A) is the most common internal modification made to eukaryotic mRNA and is involved in post-transcriptional control of gene expression. When dysregulated, m6A has been linked to a variety of diseases, including cancer. Unlike other RNA methyltransferases, m6A conversion is catalyzed by a multi-protein writer complex with only one catalytic subunit. So why is the m6A writer complex composed of so many proteins? This Unsolved Mystery explores the possible functions of the proteins of the m6A writer complex and discusses why it might require multiple subunits. Understanding the roles of these proteins could provide insight into how m6A is regulated and reveal new strategies for targeting diseases linked to m6A dysregulation.