New RNA Modification Found

Harvard chemists have discovered a new type of RNA modification—addition of a geranyl group, which is a type of lipid (Nat. Chem. Biol., DOI: 10.1038/nchembio.1070). David R. Liu and coworkers tweaked an existing method for screening small- molecule-RNA conjugates so that they could separate and isolate hydrophobic modifications. They found two geranylated nucleosides, which are the first known oligoisoprene modifications of RNA and are the most hydrophobic modifications yet identified. The geranylation occurs on the sulfur of a modified thiouridine. Liu and coworkers found that these modified nucleosides occur at the first position of the anticodon (recognition portion) of three bacterial transfer RNAs—one for glutamate, one for lysine, and one for glutamine. At this location, geranylation affects codon recognition properties. The researchers found that the enzyme SelU, whose only previously known function was selenation of thiouridine, is also responsible for the geranylation. Geranylation appears to be an alternative to selenation at low selenium concentrations. “The chemical diversity of RNA is much richer than we anticipated just a few years ago,” Liu says. “Additional small- molecule-RNA conjugates almost certainly remain to be characterized.”