Cotranscriptional folding of a riboswitch at nucleotide resolution

Kyle E. Watters, Eric J. Strobel, Angela M. Yu, John T. Lis, Julius B. Lucks

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

RNAs can begin to fold immediately as they emerge from RNA polymerase. During cotranscriptional folding, interactions between nascent RNAs and ligands are able to direct the formation of alternative RNA structures, a feature exploited by noncoding RNAs called riboswitches to make gene-regulatory decisions. Despite their importance, cotranscriptional folding pathways have yet to be uncovered with sufficient resolution to reveal how cotranscriptional folding governs RNA structure and function. To access cotranscriptional folding at nucleotide resolution, we extended selective 2′-hydroxyl acylation analyzed by primer-extension sequencing (SHAPE-seq) to measure structural information of nascent RNAs during transcription. Using cotranscriptional SHAPE-seq, we determined how the cotranscriptional folding pathway of the Bacillus cereus crcB fluoride riboswitch undergoes a ligand-dependent bifurcation that delays or promotes terminator formation via a series of coordinated structural transitions. Our results directly link cotranscriptional RNA folding to a genetic decision and establish a framework for cotranscriptional analysis of RNA structure at nucleotide resolution.

Original languageEnglish (US)
Pages (from-to)1124-1131
Number of pages8
JournalNature Structural and Molecular Biology
Volume23
Issue number12
DOIs
StatePublished - Dec 1 2016

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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