Nat. Struct. Mol. Biol. 10.1038/nsmb.3176

Credit: NAT. STRUCT. MOL. BIOL.

7SK is a small nuclear RNA (snRNA) that, as part of a specific small nuclear ribonucleoprotein (snRNP) complex, regulates promoter-proximal pausing during transcription. Using a series of genome-wide RNA profiling technologies, Flynn et al. now identify an additional role for 7SK in controlling transcription at enhancer elements. Using chromatin-RNA pulldown and sequencing techniques, the authors showed that 7SK RNA is associated with active RNA polymerase II transcription sites in diverse mammalian cell types. Distinct profiles of proteins are associated with 7SK at promoters, typical enhancer (TE) and super enhancer (SE) elements. 7SK depletion experiments highlighted 7SK's role in regulating transcriptional abundance and preventing DNA damage at SEs, and chromatin isolation by RNA purification mass spectrometry (ChIRP-MS) revealed that 7SK forms a cellular complex with BAF, a well-characterized SWI/SNF family chromatin-remodeling factor. In vivo click-selective 2′-hydroxyl acylation and profiling experiments (icSHAPE) demonstrated that 7SK adopts a distinct RNA secondary structure that enables its specific binding to BAF. Further experiments showed that the 7SK-BAF snRNP is localized at enhancers by an acetyllysine-bromodomain interaction, where BAF exerts its transcriptionally repressive effects by nucleosome repositioning. Taken together, the study highlights that 7SK snRNA (and likely other snRNAs) may provide versatile scaffolds for targeting regulatory proteins to distinct chromatin sites in the genome.