Structural transitions in the RNA 7SK 5' hairpin and their effect on HEXIM binding

Nucleic Acids Res. 2020 Jan 10;48(1):373-389. doi: 10.1093/nar/gkz1071.


7SK RNA, as part of the 7SK ribonucleoprotein complex, is crucial to the regulation of transcription by RNA-polymerase II, via its interaction with the positive transcription elongation factor P-TEFb. The interaction is induced by binding of the protein HEXIM to the 5' hairpin (HP1) of 7SK RNA. Four distinct structural models have been obtained experimentally for HP1. Here, we employ computational methods to investigate the relative stability of these structures, transitions between them, and the effects of mutations on the observed structural ensembles. We further analyse the results with respect to mutational binding assays, and hypothesize a mechanism for HEXIM binding. Our results indicate that the dominant structure in the wild type exhibits a triplet involving the unpaired nucleotide U40 and the base pair A43-U66 in the GAUC/GAUC repeat. This conformation leads to an open major groove with enough potential binding sites for peptide recognition. Sequence mutations of the RNA change the relative stability of the different structural ensembles. Binding affinity is consequently lost if these changes alter the dominant structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Humans
  • Molecular Dynamics Simulation
  • Nucleic Acid Conformation
  • Nucleotide Motifs
  • Peptides / genetics
  • Peptides / metabolism
  • Positive Transcriptional Elongation Factor B / chemistry*
  • Positive Transcriptional Elongation Factor B / genetics
  • Positive Transcriptional Elongation Factor B / metabolism
  • Protein Binding
  • RNA Polymerase II / chemistry*
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • RNA, Small Cytoplasmic / chemistry*
  • RNA, Small Cytoplasmic / genetics
  • RNA, Small Cytoplasmic / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Thermodynamics
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*


  • HEXIM1 protein, human
  • Peptides
  • RNA, Small Cytoplasmic
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • Transcription Factors
  • Positive Transcriptional Elongation Factor B
  • RNA Polymerase II