Structural basis for mutually exclusive co-transcriptional nuclear cap-binding complexes with either NELF-E or ARS2.
Schulze, W.M., Cusack, S.(2017) Nat Commun 8: 1302-1302
- PubMed: 29101316 
- DOI: https://doi.org/10.1038/s41467-017-01402-w
- Primary Citation of Related Structures:  
5OO6, 5OOB - PubMed Abstract: 
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.
Organizational Affiliation: 
European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042, Grenoble Cedex 9, France.