Unraveling the RNA Modification Code with Mass Spectrometry
The discovery and analysis of modifications on proteins and nucleic acids has provided functional information that has rapidly accelerated the field of epigenetics. While protein post-translational modifications (PTMs), especially on histones, have been highlighted as critical components of epigenetics, the posttranscriptional modification of RNA has been a subject of more recently emergent interest. Multiple RNA modifications have been known to be present in tRNA and rRNA since the 1960s, but the exploration of mRNA, small RNA, and inducible tRNA modifications remains nascent. Sequencing based methods have been used to create epitranscriptome maps of m6A, m5C, hm5C, pseudouridine and inosine, however, these methods have many limitations. Here, we discuss the application of mass spectrometry (MS) to the study of RNA modifications and their interactions in the past, present, and future.