Deciphering RNA modifications at base resolution: from chemistry to biology

Nearly 200 distinct chemical modifications of RNAs have been discovered to date. Their analysis via direct methods has been possible in abundant RNA species, such as ribosomal, transfer or viral RNA, since several decades. However, their analysis in less abundant RNAs species, especially cellular messenger RNAs, was rendered possible only recently with the advent of high throughput sequencing techniques. Given the growing biomedical interest of the proteins that write, erase and read RNA modifications, ingenious new methods to enrich and identify RNA modifications at base resolution have been implemented, and more efforts are underway to render them more quantitative. Here, we review several crucial modification-specific (bio)chemical approaches and discuss their advantages and shortcomings for exploring the epitranscriptome.