Multiple interactions between RNA polymerase I, TIF-IA and TAF(I) subunits regulate preinitiation complex assembly at the ribosomal gene promoter

EMBO Rep. 2002 Nov;3(11):1082-7. doi: 10.1093/embo-reports/kvf212. Epub 2002 Oct 22.


In mammals, growth-dependent regulation of rRNA synthesis is brought about by the transcription initiation factor TIF-IA. TIF-IA is associated with a fraction of the TBP-containing factor TIF-IB/SL1 and the initiation-competent form of RNA polymerase I (Pol I). We investigated the mechanisms that down-regulate cellular pre-rRNA synthesis and demonstrate that nutrient starvation, density arrest and protein synthesis inhibitors inactivate TIF-IA and impair the association of TIF-IA with Pol I. Moreover, we used a panel of TIF-IA deletion mutants to map the domains that mediate the interaction of TIF-IA with Pol I and TIF-IB/SL1. We found that amino acids 512-609 interact with two subunits of Pol I, RPA43 and PAF67, whereas a short, conserved motif (LARAK, amino acids 411-415) is required for the association of TIF-IA with TAF(I)95 and TAF(I)68. The results uncover an interphase for essential protein-protein interactions that facilitate Pol I preinitiation complex formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Genes, Reporter
  • Genes, rRNA*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Pol1 Transcription Initiation Complex Proteins / genetics
  • Pol1 Transcription Initiation Complex Proteins / metabolism*
  • Promoter Regions, Genetic*
  • Protein Subunits / metabolism
  • RNA Polymerase I / genetics
  • RNA Polymerase I / metabolism*
  • RNA, Ribosomal / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Pol1 Transcription Initiation Complex Proteins
  • Protein Subunits
  • RNA, Ribosomal
  • RRN3 protein, human
  • Recombinant Fusion Proteins
  • Transcription Factors
  • RNA Polymerase I

Associated data

  • GENBANK/AJ272050