Journal Article

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

García-Sastre, Adolfo, Gazzara, Matthew, Haddad, Christina, Tolbert, Blanton S., Aksenova, Vasilisa, Rex, Emily A., Batten, Kimberly, Dasso, Mary, Fontoura, Beatriz M. A., Aslam, Sadaf, Shay, Jerry W., Bhat, Prasanna, Cagatay, Tolga, Arnaoutov, Alexei, El Zahed, Sara S., Gao, Shengyan, Zhong, Hualin, Lynch, Kristen W., Esparza, Matthew

2023

Overview

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 TR anscription and EX port 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. Here, Bhat et al. show that Influenza A virus mRNAs are exported from the nucleus via the nucleoporin Tpr and the mRNA export complex TREX-2. These mRNAs have low exon number, high mean exon length, and low GC content. A 45-nucleotide RNA signal can mediate export via TREX-2.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 14 / 14/32 / 3' Untranslated regions / 38 / 38/109 / 38/77 / 38/91 / 631/326/596/1578 / 631/326/88 / 631/80/389/2052 / Active Transport, Cell Nucleus - genetics / Biodegradation / Cell Nucleus - metabolism / Exons / Exports / Humanities and Social Sciences / Humans / Influenza / Influenza A / Influenza, Human - metabolism / multidisciplinary / Nuclear Pore - genetics / Nuclear Pore - metabolism / Nuclear Pore Complex Proteins - metabolism / Nuclear pores / Nuclear Proteins - metabolism / Nuclear transport / Nucleoporins / Nucleotides / Orthomyxoviridae - genetics / Proteins / RNA transport / RNA Transport - genetics / RNA viruses / RNA, Messenger - genetics / RNA, Messenger - metabolism / Science / Science (multidisciplinary) / Viruses / Yeast