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

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  • Wiebke Manuela Schulze

    (European Molecular Biology Laboratory, Grenoble Outstation
    Ruprecht-Karls University of Heidelberg)

  • Stephen Cusack

    (European Molecular Biology Laboratory, Grenoble Outstation)

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.

Suggested Citation

  • Wiebke Manuela Schulze & Stephen Cusack, 2017. "Structural basis for mutually exclusive co-transcriptional nuclear cap-binding complexes with either NELF-E or ARS2," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01402-w
    DOI: 10.1038/s41467-017-01402-w
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    Cited by:

    1. Ross A. Cordiner & Yuhui Dou & Rune Thomsen & Andrii Bugai & Sander Granneman & Torben Heick Jensen, 2023. "Temporal-iCLIP captures co-transcriptional RNA-protein interactions," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Anne-Emmanuelle Foucher & Leila Touat-Todeschini & Ariadna B. Juarez-Martinez & Auriane Rakitch & Hamida Laroussi & Claire Karczewski & Samira Acajjaoui & Montserrat Soler-López & Stephen Cusack & Cam, 2022. "Structural analysis of Red1 as a conserved scaffold of the RNA-targeting MTREC/PAXT complex," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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