TY - JOUR
T1 - Influenza virus mRNAs encode determinants for nuclear export via the cellular TREX-2 complex
AU - Bhat, Prasanna
AU - Aksenova, Vasilisa
AU - Gazzara, Matthew
AU - Rex, Emily A.
AU - Aslam, Sadaf
AU - Haddad, Christina
AU - Gao, Shengyan
AU - Esparza, Matthew
AU - Cagatay, Tolga
AU - Batten, Kimberly
AU - El Zahed, Sara S.
AU - Arnaoutov, Alexei
AU - Zhong, Hualin
AU - Shay, Jerry W.
AU - Tolbert, Blanton S.
AU - Dasso, Mary
AU - Lynch, Kristen W.
AU - García-Sastre, Adolfo
AU - Fontoura, Beatriz M.A.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85153554269&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-37911-0
DO - 10.1038/s41467-023-37911-0
M3 - Article
C2 - 37085480
AN - SCOPUS:85153554269
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2304
ER -