Multiple interactions between RNA polymerase I, TIF-IA and TAF(I) subunits regulate preinitiation complex assembly at the ribosomal gene promoter.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Cell Line, Genes, Reporter, Genes, rRNA, Humans, Mice, Molecular Sequence Data, Pol1 Transcription Initiation Complex Proteins, Promoter Regions, Genetic, Protein Subunits, RNA Polymerase I, RNA, Ribosomal, Recombinant Fusion Proteins, Sequence Alignment, Transcription Factors
Amino Acid Sequence, Animals, Cell Line, Genes, Reporter, Genes, rRNA, Humans, Mice, Molecular Sequence Data, Pol1 Transcription Initiation Complex Proteins, Promoter Regions, Genetic, Protein Subunits, RNA Polymerase I, RNA, Ribosomal, Recombinant Fusion Proteins, Sequence Alignment, Transcription Factors
EMBO Rep.
Date: Nov. 01, 2002
PubMed ID: 12393749
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