In vivo dynamics of RNA polymerase II transcription

Nat Struct Mol Biol. 2007 Sep;14(9):796-806. doi: 10.1038/nsmb1280. Epub 2007 Aug 5.

Abstract

We imaged transcription in living cells using a locus-specific reporter system, which allowed precise, single-cell kinetic measurements of promoter binding, initiation and elongation. Photobleaching of fluorescent RNA polymerase II revealed several kinetically distinct populations of the enzyme interacting with a specific gene. Photobleaching and photoactivation of fluorescent MS2 proteins used to label nascent messenger RNAs provided sensitive elongation measurements. A mechanistic kinetic model that fits our data was validated using specific inhibitors. Polymerases elongated at 4.3 kilobases min(-1), much faster than previously documented, and entered a paused state for unexpectedly long times. Transcription onset was inefficient, with only 1% of polymerase-gene interactions leading to completion of an mRNA. Our systems approach, quantifying both polymerase and mRNA kinetics on a defined DNA template in vivo with high temporal resolution, opens new avenues for studying regulation of transcriptional processes in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • DNA Primers
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kinetics
  • Phosphorylation
  • Photochemistry
  • RNA Polymerase II / genetics*
  • RNA Polymerase II / metabolism
  • Transcription, Genetic* / drug effects

Substances

  • DNA Primers
  • RNA Polymerase II