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Selective 2′‐hydroxyl acylation analyzed by primer extension ( SHAPE ) provides information on  RNA  structure at single‐nucleotide resolution. It is most often used in conjunction with  RNA  secondary structure prediction algorithms as a probabilistic or thermodynamic restraint. With the recent advent of ultra‐high‐throughput approaches for collecting  SHAPE  data, the applications of this technology are extending beyond structure prediction. In this review, we discuss recent applications of  SHAPE  data in the transcriptomic context and how this new experimental paradigm is changing our understanding of these experiments and  RNA  folding in general.  SHAPE  experiments probe both the secondary and tertiary structure of an  RNA , suggesting that model‐free approaches for within and comparative  RNA  structure analysis can provide significant structural insight without the need for a full structural model. New methods incorporating  SHAPE  at different nucleotide resolutions are required to parse these transcriptomic data sets to transcend secondary structure modeling with global structural metrics. These ‘multiscale’ approaches provide deeper insights into  RNA  global structure, evolution, and function in the cell.  WIREs RNA  2017, 8:e1374. doi: 10.1002/wrna.1374  This article is categorized under:  RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry  RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution  RNA Evolution and Genomics > Computational Analyses of RNA

Transcending the prediction paradigm: novel applications of SHAPE to RNA function and evolution