Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced Viral M1 mRNA

Journal of Virology
Carina F PereiraPaul Digard

Abstract

Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using fluorescent in situ hybridization to monitor segment 7 mRNA localization, we found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid transfection and in mutant virus-infected cells. This effect was independent of any major effect on steady-state levels of segment 7 mRNA or splicing but corresponded to a ∼5-fold reduction in the accumulation of M1. A similar defect in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain and effector domain. Furthermore, while wild-type NS1 interacted...Continue Reading

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Citations

Apr 3, 2020·PLoS Pathogens·Matthew EsparzaBeatriz M A Fontoura
Apr 11, 2019·Nature Communications·Marta AlenquerMaria João Amorim
Sep 17, 2020·Viruses·Jón Pol GalesMaria Dimitrova
Sep 16, 2018·Viruses·Ahmed MostafaStephan Pleschka
Sep 20, 2018·BMC Research Notes·Carina F PereiraPaul Digard
Nov 28, 2020·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Shalini Guha, Sukesh R Bhaumik
Aug 10, 2021·Frontiers in Microbiology·Jingjing LiMeili Li

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Methods Mentioned

BETA
transfection
confocal microscopy
pulldown
affinity purification
PCR
transfections

Software Mentioned

Licor Odyssey

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