Transcriptional properties of mammalian elongin A and its role in stress response

J Biol Chem. 2013 Aug 23;288(34):24302-15. doi: 10.1074/jbc.M113.496703. Epub 2013 Jul 3.

Abstract

Elongin A was shown previously to be capable of potently activating the rate of RNA polymerase II (RNAPII) transcription elongation in vitro by suppressing transient pausing by the enzyme at many sites along DNA templates. The role of Elongin A in RNAPII transcription in mammalian cells, however, has not been clearly established. In this report, we investigate the function of Elongin A in RNAPII transcription. We present evidence that Elongin A associates with the IIO form of RNAPII at sites of newly transcribed RNA and is relocated to dotlike domains distinct from those containing RNAPII when cells are treated with the kinase inhibitor 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole. Significantly, Elongin A is required for maximal induction of transcription of the stress response genes ATF3 and p21 in response to several stimuli. Evidence from structure-function studies argues that Elongin A transcription elongation activity, but not its ubiquitination activity, is most important for its function in induction of transcription of ATF3 and p21. Taken together, our data provide new insights into the function of Elongin A in RNAPII transcription and bring to light a previously unrecognized role for Elongin A in the regulation of stress response genes.

Keywords: ATF3; Elongin A; Gene Regulation; Mammal; RNA Polymerase II; Stress Response; Transcription Elongation Factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 3 / biosynthesis
  • Activating Transcription Factor 3 / genetics
  • Animals
  • Dichlororibofuranosylbenzimidazole / pharmacology
  • Elongin
  • Enzyme Inhibitors / pharmacology
  • HeLa Cells
  • Humans
  • Mice
  • RNA Polymerase II / antagonists & inhibitors
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • Rats
  • Stress, Physiological / drug effects
  • Stress, Physiological / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Initiation, Genetic / drug effects
  • Transcription Initiation, Genetic / physiology*

Substances

  • ATF3 protein, human
  • Activating Transcription Factor 3
  • Atf3 protein, mouse
  • Atf3 protein, rat
  • ELOA protein, human
  • Eloa protein, mouse
  • Eloa protein, rat
  • Elongin
  • Enzyme Inhibitors
  • Transcription Factors
  • Dichlororibofuranosylbenzimidazole
  • RNA Polymerase II