Recognition of RNA polymerase II carboxy-terminal domain by 3'-RNA-processing factors

Nature. 2004 Jul 8;430(6996):223-6. doi: 10.1038/nature02679.

Abstract

During transcription, RNA polymerase (Pol) II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing by the carboxy-terminal domain (CTD) of Pol II, which consists of up to 52 repeats of the sequence Tyr 1-Ser 2-Pro 3-Thr 4-Ser 5-Pro 6-Ser 7 (refs 1, 2). After phosphorylation, the CTD binds tightly to a conserved CTD-interacting domain (CID) present in the proteins Pcf11 and Nrd1, which are essential and evolutionarily conserved factors for polyadenylation-dependent and -independent 3'-RNA processing, respectively. Here we describe the structure of a Ser 2-phosphorylated CTD peptide bound to the CID domain of Pcf11. The CTD motif Ser 2-Pro 3-Thr 4-Ser 5 forms a beta-turn that binds to a conserved groove in the CID domain. The Ser 2 phosphate group does not make direct contact with the CID domain, but may be recognized indirectly because it stabilizes the beta-turn with an additional hydrogen bond. Iteration of the peptide structure results in a compact beta-spiral model of the CTD. The model suggests that, during the mRNA transcription-processing cycle, compact spiral regions in the CTD are unravelled and regenerated in a phosphorylation-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Conserved Sequence
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Polymerase II / chemistry*
  • RNA Polymerase II / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA-Binding Proteins
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Substrate Specificity
  • mRNA Cleavage and Polyadenylation Factors / chemistry*
  • mRNA Cleavage and Polyadenylation Factors / metabolism*

Substances

  • Fungal Proteins
  • NRD1 protein, S cerevisiae
  • PCF11 protein, S cerevisiae
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • Saccharomyces cerevisiae Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • RNA Polymerase II

Associated data

  • PDB/1SZ9
  • PDB/1SZA