An Rpb4/Rpb7-like complex in yeast RNA polymerase III contains the orthologue of mammalian CGRP-RCP

Mol Cell Biol. 2003 Jan;23(1):195-205. doi: 10.1128/MCB.23.1.195-205.2003.


The essential C17 subunit of yeast RNA polymerase (Pol) III interacts with Brf1, a component of TFIIIB, suggesting a role for C17 in the initiation step of transcription. The protein sequence of C17 (encoded by RPC17) is conserved from yeasts to humans. However, mammalian homologues of C17 (named CGRP-RCP) are known to be involved in a signal transduction pathway related to G protein-coupled receptors, not in transcription. In the present work, we first establish that human CGRP-RCP is the genuine orthologue of C17. CGRP-RCP was found to functionally replace C17 in Deltarpc17 yeast cells; the purified mutant Pol III contained CGRP-RCP and had a decreased specific activity but initiated faithfully. Furthermore, CGRP-RCP was identified by mass spectrometry in a highly purified human Pol III preparation. These results suggest that CGRP-RCP has a dual function in mammals. Next, we demonstrate by genetic and biochemical approaches that C17 forms with C25 (encoded by RPC25) a heterodimer akin to Rpb4/Rpb7 in Pol II. C17 and C25 were found to interact genetically in suppression screens and physically in coimmunopurification and two-hybrid experiments. Sequence analysis and molecular modeling indicated that the C17/C25 heterodimer likely adopts a structure similar to that of the archaeal RpoE/RpoF counterpart of the Rpb4/Rpb7 complex. These RNA polymerase subunits appear to have evolved to meet the distinct requirements of the multiple forms of RNA polymerases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Dimerization
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Humans
  • Macromolecular Substances
  • Mammals
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Conformation
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • RNA Polymerase III / genetics
  • RNA Polymerase III / metabolism*
  • Receptors, Calcitonin Gene-Related Peptide / genetics
  • Receptors, Calcitonin Gene-Related Peptide / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Sigma Factor / chemistry
  • Sigma Factor / genetics
  • Sigma Factor / metabolism
  • Suppression, Genetic
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Yeasts / genetics
  • Yeasts / metabolism


  • Archaeal Proteins
  • Bacterial Proteins
  • CRCP protein, human
  • FliA protein, Bacteria
  • Fungal Proteins
  • Macromolecular Substances
  • Receptors, Calcitonin Gene-Related Peptide
  • Saccharomyces cerevisiae Proteins
  • Sigma Factor
  • Transcription Factors
  • sporulation-specific sigma factors
  • RNA Polymerase II
  • RPB4 protein, S cerevisiae
  • RPB7 protein, S cerevisiae
  • RNA Polymerase III