Spitale, R.C. et al. Nat. Chem. Biol. 9, 18–20 (2013).

RNA molecules in the cell form complex secondary and tertiary structures that can provide clues to their specific functional roles. RNA secondary structures can be mapped on a broad scale with a method called selected 2'-hydroxyl acylation analyzed by primer extension, or SHAPE. In new work, Spitale et al. moved SHAPE into living cells, with the design and testing of new 2'-hydroxyl acylation reagents that are water soluble at high concentrations. The improved approach allowed them to characterize the secondary structure of 5S ribosomal RNA (rRNA) in living mouse embryonic stem cells, human cancer cells, fruit fly cells, yeast and Escherichia coli. A comparison of SHAPE results from probing 5S rRNA structure in vivo versus in vitro showed that RNA-RNA and RNA-protein interactions are important for docking the 5S rRNA into the ribosome.