Structural basis for mutually exclusive co-transcriptional nuclear cap-binding complexes with either NELF-E or ARS2

Nat Commun. 2017 Nov 3;8(1):1302. doi: 10.1038/s41467-017-01402-w.


Pol II transcribes diverse classes of RNAs that need to be directed into the appropriate nuclear maturation pathway. All nascent Pol II transcripts are 5'-capped and the cap is immediately sequestered by the nuclear cap-binding complex (CBC). Mutually exclusive interactions of CBC with different partner proteins have been implicated in transcript fate determination. Here, we characterise the direct interactions between CBC and NELF-E, a subunit of the negative elongation factor complex, ARS2 and PHAX. Our biochemical and crystal structure results show that the homologous C-terminal peptides of NELF-E and ARS2 bind identically to CBC and in each case the affinity is enhanced when CBC is bound to a cap analogue. Furthermore, whereas PHAX forms a complex with CBC and ARS2, NELF-E binding to CBC is incompatible with PHAX binding. We thus define two mutually exclusive complexes CBC-NELF-E and CBC-ARS2-PHAX, which likely act in respectively earlier and later phases of transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Models, Molecular
  • Nuclear Cap-Binding Protein Complex / chemistry*
  • Nuclear Cap-Binding Protein Complex / metabolism
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Nucleocytoplasmic Transport Proteins / chemistry
  • Nucleocytoplasmic Transport Proteins / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • RNA Cap Analogs / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism
  • Transcription, Genetic


  • Nuclear Cap-Binding Protein Complex
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • PHAX protein, human
  • Phosphoproteins
  • RNA Cap Analogs
  • Recombinant Proteins
  • SRRT protein, human
  • Transcription Factors
  • negative elongation factor
  • 7-methylguanosine triphosphate