Deciphering nucleic acid modifications by chemical derivatization-mass spectrometry analysis

Now increasing chemical modifications are discovered on genomic DNA and RNA. Up to date, more than 150 chemical modifications are identified in nucleic acids. These chemical modifications do not change the sequence of DNA and RNA, but alter their structures and biochemical properties, and eventually control or regulate the spatial and temporal expression of genes. Elucidation of the functional roles of these modifications is vital to our understanding of living organisms. However, the modifications in DNA and RNA generally have extremely low abundance in vivo. Therefore, sensitive and specific detection methods are essential to decipher the functional roles of these modifications. Chemical derivatization in combination with mass spectrometry (MS) analysis has been proved to be a promising strategy to efficiently analyze these modifications in DNA and RNA. In the last several years, many chemical derivatization-MS-based analytical methods were established for the sensitive and effective analysis of nucleic acid modifications. In this review, we summarize the recent advances for deciphering modifications in DNA and RNA by chemical derivatization-MS analysis. We hope this review can stimulate the future studies of DNA and RNA modifications.