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

TitleStructural transitions in the RNA 7SK 5' hairpin and their effect on HEXIM binding
Publication TypeJournal Article
Year of Publication2020
AuthorsRöder K, Stirnemann G, Dock-Bregeon A-C, Wales DJ, Pasquali S
JournalNucleic Acids Res
Volume48
Pagination373-389
Date Published01
Abstract

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.

DOI10.1093/nar/gkz1071
Citation Key2020|2140
PubMed ID31732748