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

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 Arnaoutov, Hualin Zhong, Jerry W. Shay, Blanton S. Tolbert, Mary Dasso, Kristen W. Lynch, Adolfo García-Sastre, Beatriz M.A. Fontoura

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Article number2304
JournalNature Communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

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