RNA polymerase pausing at a protein roadblock can enhance transcriptional interference by promoter occlusion

FEBS Lett. 2019 May;593(9):903-917. doi: 10.1002/1873-3468.13365. Epub 2019 Mar 29.

Abstract

Convergent promoters exert transcriptional interference (TI) by several mechanisms including promoter occlusion, where elongating RNA polymerases (RNAPs) block access to a promoter. Here, we tested whether pausing of RNAPs by obstructive DNA-bound proteins can enhance TI by promoter occlusion. Using the Lac repressor as a 'roadblock' to induce pausing over a target promoter, we found only a small increase in TI, with mathematical modelling suggesting that rapid termination of the stalled RNAP was limiting the occlusion effect. As predicted, the roadblock-enhanced occlusion was significantly increased in the absence of the Mfd terminator protein. Thus, protein roadblocking of RNAP may cause pause-enhanced occlusion throughout genomes, and the removal of stalled RNAP may be needed to minimize unwanted TI.

Keywords: RNAP pausing; bacteriophage; mathematical modelling; promoter occlusion; transcriptional interference; transcriptional roadblocking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophages / genetics
  • DNA-Directed RNA Polymerases / metabolism*
  • Genes, Reporter / genetics
  • Models, Biological
  • Promoter Regions, Genetic / genetics*
  • Transcription, Genetic / genetics*

Substances

  • DNA-Directed RNA Polymerases

Associated data

  • GENBANK/NC_001317.1