Structural perspective on mutations affecting the function of multisubunit RNA polymerases

Microbiol Mol Biol Rev. 2006 Mar;70(1):12-36. doi: 10.1128/MMBR.70.1.12-36.2006.

Abstract

High-resolution crystallographic structures of multisubunit RNA polymerases (RNAPs) have increased our understanding of transcriptional mechanisms. Based on a thorough review of the literature, we have compiled the mutations affecting the function of multisubunit RNA polymerases, many of which having been generated and studied prior to the publication of the first high-resolution structure, and highlighted the positions of the altered amino acids in the structures of both the prokaryotic and eukaryotic enzymes. The observations support many previous hypotheses on the transcriptional process, including the implication of the bridge helix and the trigger loop in the processivity of RNAP, the importance of contacts between the RNAP jaw-lobe module and the downstream DNA in the establishment of a transcription bubble and selection of the transcription start site, the destabilizing effects of ppGpp on the open promoter complex, and the link between RNAP processivity and termination. This study also revealed novel, remarkable features of the RNA polymerase catalytic mechanisms that will require additional investigation, including the putative roles of fork loop 2 in the establishment of a transcription bubble, the trigger loop in start site selection, and the uncharacterized funnel domain in RNAP processivity.

Publication types

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

MeSH terms

  • Amino Acid Substitution
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • DNA-Directed RNA Polymerases / chemistry*
  • DNA-Directed RNA Polymerases / genetics*
  • DNA-Directed RNA Polymerases / metabolism
  • Drug Resistance / genetics
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Mutation
  • Protein Conformation
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Transcription Initiation Site

Substances

  • Bacterial Proteins
  • Fungal Proteins
  • RNA Polymerase II
  • DNA-Directed RNA Polymerases