Large-scale allosteric switch in the human 7SK RNA revealed by deconvolution and annotation of ribonucleic conformational ensembles (DANCE-MaP)

7SK is an essential non-coding RNA that regulates eukaryotic transcription by sequestering positive transcription elongation factor b (P-TEFb). 7SK regulatory function likely entails changes in RNA structure, but characterizing dynamic RNA-protein complexes in cells has remained a critical challenge. We describe a new chemical probing strategy (DANCE-MaP) that uses maximum likelihood deconvolution and probabilistic read assignment to define simultaneously (i) per-nucleotide reactivity profiles, (ii) direct base pairing interactions, and (iii) tertiary and higher-order interactions for each conformation of multi-state RNA structural ensembles, all from a single experiment. We show that human 7SK RNA, despite significant heterogeneity, intrinsically codes for a large-scale structural switch that couples dissolution of the P-TEFb binding site to structural remodeling at distal release factor binding sites. The 7SK structural equilibrium is regulated by cell type and dynamically shifts in response to stress. We further demonstrate an antisense oligonucleotide strategy for inducing 7SK structural switching to modulate transcription in cells. Collectively, our data indicate that the 7SK structural ensemble functions as an integrator of diverse cellular signals to control transcription elongation.