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Influenza virus mRNAs encode determinants for nuclear export via the cellular TREX-2 complex

Author

Listed:
  • Prasanna Bhat

    (University of Texas Southwestern Medical Center)

  • Vasilisa Aksenova

    (National Institutes of Health)

  • Matthew Gazzara

    (University of Pennsylvania)

  • Emily A. Rex

    (University of Texas Southwestern Medical Center)

  • Sadaf Aslam

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Christina Haddad

    (Case Western Reserve University)

  • Shengyan Gao

    (University of Texas Southwestern Medical Center)

  • Matthew Esparza

    (University of Texas Southwestern Medical Center)

  • Tolga Cagatay

    (University of Texas Southwestern Medical Center)

  • Kimberly Batten

    (University of Texas Southwestern Medical Center)

  • Sara S. El Zahed

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Alexei Arnaoutov

    (National Institutes of Health)

  • Hualin Zhong

    (Hunter College)

  • Jerry W. Shay

    (University of Texas Southwestern Medical Center)

  • Blanton S. Tolbert

    (Case Western Reserve University)

  • Mary Dasso

    (National Institutes of Health)

  • Kristen W. Lynch

    (University of Pennsylvania)

  • Adolfo García-Sastre

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Beatriz M. A. Fontoura

    (University of Texas Southwestern Medical Center)

Abstract

Nuclear export of influenza A virus (IAV) mRNAs occurs through the nuclear pore complex (NPC). Using the Auxin-Induced Degron (AID) system to rapidly degrade proteins, we show that among the nucleoporins localized at the nucleoplasmic side of the NPC, TPR is the key nucleoporin required for nuclear export of influenza virus mRNAs. TPR recruits the TRanscription and EXport complex (TREX)−2 to the NPC for exporting a subset of cellular mRNAs. By degrading components of the TREX-2 complex (GANP, Germinal-center Associated Nuclear Protein; PCID2, PCI domain containing 2), we show that influenza mRNAs require the TREX-2 complex for nuclear export and replication. Furthermore, we found that cellular mRNAs whose export is dependent on GANP have a small number of exons, a high mean exon length, long 3’ UTR, and low GC content. Some of these features are shared by influenza virus mRNAs. Additionally, we identified a 45 nucleotide RNA signal from influenza virus HA mRNA that is sufficient to mediate GANP-dependent mRNA export. Thus, we report a role for the TREX-2 complex in nuclear export of influenza mRNAs and identified RNA determinants associated with the TREX-2-dependent mRNA export.

Suggested Citation

  • Prasanna Bhat & Vasilisa Aksenova & Matthew Gazzara & Emily A. Rex & Sadaf Aslam & Christina Haddad & Shengyan Gao & Matthew Esparza & Tolga Cagatay & Kimberly Batten & Sara S. El Zahed & Alexei Arnao, 2023. "Influenza virus mRNAs encode determinants for nuclear export via the cellular TREX-2 complex," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37911-0
    DOI: 10.1038/s41467-023-37911-0
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    1. Vasilisa Aksenova & Alexandra Smith & Hangnoh Lee & Prasanna Bhat & Caroline Esnault & Shane Chen & James Iben & Ross Kaufhold & Ka Chun Yau & Carlos Echeverria & Beatriz Fontoura & Alexei Arnaoutov &, 2020. "Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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