NAD-capped RNAs – a redox cofactor meets RNA

RNA modifications immensely expand the diversity of the transcriptome, thereby influencing the function, localization, and stability of RNA. One prominent example of an RNA modification is the eukaryotic cap located at the 5′ terminus of mRNAs. Interestingly, the redox cofactor NAD can be incorporated into RNA by RNA polymerase in vitro. The existence of NAD-modified RNAs in vivo was confirmed using liquid chromatography and mass spectrometry (LC-MS). In the past few years novel technologies and methods have characterized NAD as a cap-like RNA structure and enabled the investigation of NAD-capped RNAs (NAD-RNAs) in a physiological context. We highlight the identification of NAD-RNAs as well as the regulation and functions of this epitranscriptomic mark in all domains of life.