A new bacterial adenosine-derived nucleoside as an example of RNA modification damage

Abstract

The fields of RNA modification and RNA damage both exhibit a plethora of non-canonical nucleo side structures. While RNA modifications have evolved to improve RNA function, the term RNA damage implies detrimental effects. Based on stable isotope labelling and mass spectrometry, we report the identi fication and characterisation of 2-methylthio-1,N6-ethe noadenosine (ms2 ɛA), which is related to 1,N6-etheno adenine, a lesion resulting from exposure of nucleic acids to alkylating chemicals in vivo. In contrast, a sophisticated isoprene labelling scheme revealed that ms2 ɛA biogenesis involves cleavage of a prenyl moiety in the known transfer RNA (tRNA) modification 2-meth ylthio-N6-isopentenyladenosine (ms2 i 6 A). The relative abundance of ms2 ɛA in tRNAs from translating ribo somes suggests reduced function in comparison to its parent RNA modification, establishing the nature of the new structure in a newly perceived overlap of the two previously separate fields, namely an RNA modification damage.