RNA-modifying proteins as anticancer drug targets

Covalent modifications of RNA — mediated by RNA-modifying proteins (RMPs) — affect RNA stability and translation to proteins, and some of these RMPs have been implicated in cancer. Here, Copeland and colleagues review the current understanding of RNA modifications with a focus on mRNA methylation and assess the potential of RMPs as novel anticancer targets. All major biological macromolecules (DNA, RNA, proteins and lipids) undergo enzyme-catalysed covalent modifications that impact their structure, function and stability. A variety of covalent modifications of RNA have been identified and demonstrated to affect RNA stability and translation to proteins; these mechanisms of translational control have been termed epitranscriptomics. Emerging data suggest that some epitranscriptomic mechanisms are altered in human cancers as well as other human diseases. In this Review, we examine the current understanding of RNA modifications with a focus on mRNA methylation, highlight their possible roles in specific cancer indications and discuss the emerging potential of RNA-modifying proteins as therapeutic targets.