McDonald, R.I. et al. Nat. Chem. Biol. doi:10.1038/nchembio.1655 (12 October 2014).

With recent studies showing that most RNAs are noncoding but functional, methods to study such RNAs are in high demand. McDonald et al. report a set of activity-based probes to enrich and identify bioactive RNAs. Reasoning that many bioactive RNAs have nucleophilic activity, the researchers screened for small-molecule electrophiles that would covalently modify only nucleophilic RNAs and not random RNA sequences. They synthesized their most promising probes in a biotinylated form to enable streptavidin-based affinity capture of bioactive RNAs. They then incubated their cocktail of eight activity-based probes with RNA fragments from nine different organisms and used selection and sequencing to identify reactive RNAs. This led them to discover a catalytic RNA from the archaebacterium Aeropyrum pernix, which shows promise as a tool for selectively labeling RNA with small-molecule tags.