A Two-Way Street: Regulatory Interplay between RNA Polymerase and Nascent RNA Structure

Trends Biochem Sci. 2016 Apr;41(4):293-310. doi: 10.1016/j.tibs.2015.12.009. Epub 2016 Jan 25.


The vectorial (5'-to-3' at varying velocity) synthesis of RNA by cellular RNA polymerases (RNAPs) creates a rugged kinetic landscape, demarcated by frequent, sometimes long-lived, pauses. In addition to myriad gene-regulatory roles, these pauses temporally and spatially program the co-transcriptional, hierarchical folding of biologically active RNAs. Conversely, these RNA structures, which form inside or near the RNA exit channel, interact with the polymerase and adjacent protein factors to influence RNA synthesis by modulating pausing, termination, antitermination, and slippage. Here, we review the evolutionary origin, mechanistic underpinnings, and regulatory consequences of this interplay between RNAP and nascent RNA structure. We categorize and rationalize the extensive linkage between the transcriptional machinery and its product, and provide a framework for future studies.

Keywords: RNA polymerase; RNA processing; RNA structure; termination and antitermination; transcriptional pausing.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Bacillus subtilis / genetics*
  • Bacillus subtilis / metabolism
  • DNA-Directed RNA Polymerases / chemistry*
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Evolution, Molecular*
  • Models, Molecular
  • Nucleic Acid Conformation
  • Peptide Elongation Factors / chemistry
  • Peptide Elongation Factors / genetics
  • Peptide Elongation Factors / metabolism
  • Protein Binding
  • Protein Folding
  • Protein Subunits / chemistry*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA / chemistry*
  • RNA / genetics
  • RNA / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Initiation, Genetic
  • Transcription Termination, Genetic
  • Transcriptional Elongation Factors / chemistry
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism


  • Escherichia coli Proteins
  • NusG protein, E coli
  • Peptide Elongation Factors
  • Protein Subunits
  • Transcription Factors
  • Transcriptional Elongation Factors
  • nusA protein, E coli
  • RNA
  • DNA-Directed RNA Polymerases