Technologies to image RNA folding exist, but they are very low resolution and cannot image the individual components of RNA rapidly enough to capture the folding processes. It has never been possible to watch with sufficient resolution how cotranscriptional folding governs RNA structure and function. Only very little is known about how RNA folds while synthesized by the cell.

Julius B. Lucks, Northwestern University, Evanston, IL, USA, and colleagues have developed a technology that provides a super high-resolution representation of RNA folding as it is being synthesized. This allows to view this crucial biological process and could potentially lead to future discoveries in basic biology, gene expression, RNA viruses, and diseases.

The technology combines a next-generation sequencing technique, which is typically used for sequencing human genomes, and a chemistry technique to turn RNA structure measurements into big data. The technique captures the RNA folding pathway in a massive dataset. Computational tools mine and organize the data. From the structural information a movie of the RNA folding process can be constructed. The team plans to make the data-analysis component open source, so researchers anywhere can use the program.

The researchers determined how the cotranscriptional folding pathway of the Bacillus cereus crcB fluoride riboswitch undergoes a ligand-dependent bifurcation that delays or promotes terminator formation via a series of coordinated structural transitions.

• Cotranscriptional folding of a riboswitch at nucleotide resolution,
  Kyle E Watters, Eric J Strobel, Angela M Yu, John T Lis, Julius B Lucks,
  Nature Struct. Molec. Biol. 2017.
  DOI: 10.1038/nsmb.3316