DksA: a critical component of the transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP

Cell. 2004 Aug 6;118(3):311-22. doi: 10.1016/j.cell.2004.07.009.

Abstract

Ribosomal RNA (rRNA) transcription is regulated primarily at the level of initiation from rRNA promoters. The unusual kinetic properties of these promoters result in their specific regulation by two small molecule signals, ppGpp and the initiating NTP, that bind to RNA polymerase (RNAP) at all promoters. We show here that DksA, a protein previously unsuspected as a transcription factor, is absolutely required for rRNA regulation. In deltadksA mutants, rRNA promoters are unresponsive to changes in amino acid availability, growth rate, or growth phase. In vitro, DksA binds to RNAP, reduces open complex lifetime, inhibits rRNA promoter activity, and amplifies effects of ppGpp and the initiating NTP on rRNA transcription, explaining the dksA requirement in vivo. These results expand our molecular understanding of rRNA transcription regulation, may explain previously described pleiotropic effects of dksA, and illustrate how transcription factors that do not bind DNA can nevertheless potentiate RNAP for regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Mutation
  • Promoter Regions, Genetic
  • Pyrophosphatases / metabolism*
  • RNA, Ribosomal / genetics*
  • RNA, Ribosomal / metabolism
  • Transcription, Genetic / physiology*

Substances

  • Amino Acids
  • Escherichia coli Proteins
  • RNA, Ribosomal
  • dksA protein, E coli
  • guanosine-3',5'-bis(diphosphate) 3'-pyrophosphatase
  • Pyrophosphatases