The transcription cycle of RNA polymerase II in living cells

J Cell Biol. 2002 Dec 9;159(5):777-82. doi: 10.1083/jcb.200206019. Epub 2002 Dec 9.

Abstract

RNA polymerase II transcribes most eukaryotic genes. Its catalytic subunit was tagged with green fluorescent protein and expressed in Chinese hamster cells bearing a mutation in the same subunit; it complemented the defect and so was functional. Photobleaching revealed two kinetic fractions of polymerase in living nuclei: approximately 75% moved rapidly, but approximately 25% was transiently immobile (association t1/2 approximately 20 min) and transcriptionally active, as incubation with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole eliminated it. No immobile but inactive fraction was detected, providing little support for the existence of a stable holoenzyme, or the slow stepwise assembly of a preinitiation complex on promoters or the nuclear substructure. Actinomycin D decreased the rapidly moving fraction, suggesting that engaged polymerases stall at intercalated molecules while others initiate. When wild-type cells containing only the endogenous enzyme were incubated with [3H]uridine, nascent transcripts became saturated with tritium with similar kinetics (t1/2 approximately 14 min). These data are consistent with a polymerase being mobile for one half to five sixths of a transcription cycle, and rapid assembly into the preinitiation complex. Then, most expressed transcription units would spend significant times unassociated with engaged polymerases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cricetinae
  • Dactinomycin / pharmacology
  • Dichlororibofuranosylbenzimidazole / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Green Fluorescent Proteins
  • Kinetics
  • Luminescent Proteins / metabolism
  • Models, Genetic
  • Mutagenesis / physiology
  • Mutation
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Periodicity
  • Photobleaching
  • RNA Polymerase II / drug effects
  • RNA Polymerase II / metabolism*
  • Temperature
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic* / drug effects

Substances

  • Luminescent Proteins
  • Nucleic Acid Synthesis Inhibitors
  • Transcription Factors
  • Green Fluorescent Proteins
  • Dactinomycin
  • Dichlororibofuranosylbenzimidazole
  • RNA Polymerase II