Region 3.2 of the sigma subunit contributes to the binding of the 3'-initiating nucleotide in the RNA polymerase active center and facilitates promoter clearance during initiation

J Biol Chem. 2006 Jul 7;281(27):18273-6. doi: 10.1074/jbc.C600060200. Epub 2006 May 10.

Abstract

Region 3.2 of the RNA polymerase sigma subunit forms a loop that protrudes toward RNA polymerase active center and partially blocks RNA exit channel. To provide some insights into the functional role of this region, we studied a deletion variant of the Escherichia coli sigma(70) subunit that lacked amino acids 513-519 corresponding to the tip of the loop. The deletion had multiple effects on transcription initiation including: (i) a significant decrease in the amount of short abortive RNAs synthesized during initiation, (ii) defects in promoter escape, (iii) loss of the contacts between the sigma subunit and the nascent RNA during initiation and, finally, (iv) dramatic increase in the K(m) value for the 3'-initiating nucleotide. At the same time, the mutation did not impair promoter opening and the binding of the 5'-initiating purine nucleotide. In summary, our data demonstrate an important role of sigma region 3.2 in the binding of initiating substrates in RNA polymerase active center and in the process of promoter clearance.

Publication types

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

MeSH terms

  • Binding Sites / genetics
  • DNA-Directed RNA Polymerases / chemistry
  • DNA-Directed RNA Polymerases / genetics*
  • DNA-Directed RNA Polymerases / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Models, Molecular
  • Promoter Regions, Genetic / genetics*
  • Sequence Deletion
  • Sigma Factor / chemistry
  • Sigma Factor / genetics*
  • Sigma Factor / metabolism
  • Structure-Activity Relationship
  • Transcription Initiation Site*
  • Transcription, Genetic*

Substances

  • Escherichia coli Proteins
  • Sigma Factor
  • RNA polymerase sigma 70
  • DNA-Directed RNA Polymerases