Transcriptional Interference in Convergent Promoters as a Means for Tunable Gene Expression

ACS Synth Biol. 2016 Dec 16;5(12):1331-1341. doi: 10.1021/acssynbio.5b00223. Epub 2016 Jul 5.

Abstract

An important goal of synthetic biology involves the extension and standardization of novel biological elements for applications in medicine and biotechnology. Transcriptional interference, occurring in sets of convergent promoters, offers a promising mechanism for building elements for the design of tunable gene regulation. Here, we investigate the transcriptional interference mechanisms of antisense roadblock and RNA polymerase traffic in a set of convergent promoters as novel modules for synthetic biology. We show examples of elements, including antisense roadblock, relative promoter strengths, interpromoter distance, and sequence content that can be tuned to give rise to repressive as well as cooperative behaviors, therefore resulting in distinct gene expression patterns. Our approach will be useful toward engineering new biological devices and will bring new insights to naturally occurring cis-antisense systems. Therefore, we are reporting a new biological tool that can be used for synthetic biology.

Keywords: RNA polymerase collision; antisense roadblock; antisense transcription; gene regulation; genetic switches; transcriptional interference.

Publication types

  • Letter

MeSH terms

  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism
  • DNA, Bacterial / genetics
  • DNA-Directed RNA Polymerases / genetics*
  • DNA-Directed RNA Polymerases / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Promoter Regions, Genetic*
  • RNA, Antisense / genetics*
  • Sequence Analysis, DNA
  • Synthetic Biology / methods*
  • Transcription, Genetic

Substances

  • Bacterial Toxins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • RNA, Antisense
  • SrnB protein, E coli
  • DNA-Directed RNA Polymerases