mRNA 3'UTR lengthening by alternative polyadenylation attenuates inflammatory responses and correlates with virulence of Influenza A virus.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 08 2023
15 08 2023
Historique:
received:
13
02
2023
accepted:
27
07
2023
medline:
17
8
2023
pubmed:
16
8
2023
entrez:
15
8
2023
Statut:
epublish
Résumé
Changes of mRNA 3'UTRs by alternative polyadenylation (APA) have been associated to numerous pathologies, but the mechanisms and consequences often remain enigmatic. By combining transcriptomics, proteomics and recombinant viruses we show that all tested strains of IAV, including A/PR/8/34(H1N1) (PR8) and A/Cal/07/2009 (H1N1) (Cal09), cause APA. We mapped the effect to the highly conserved glycine residue at position 184 (G184) of the viral non-structural protein 1 (NS1). Unbiased mass spectrometry-based analyses indicate that NS1 causes APA by perturbing the function of CPSF4 and that this function is unrelated to virus-induced transcriptional shutoff. Accordingly, IAV strain PR8, expressing an NS1 variant with weak CPSF binding, does not induce host shutoff but only APA. However, recombinant IAV (PR8) expressing NS1(G184R) lacks binding to CPSF4 and thereby also the ability to cause APA. Functionally, the impaired ability to induce APA leads to an increased inflammatory cytokine production and an attenuated phenotype in a mouse infection model. Investigating diverse viral infection models showed that APA induction is a frequent ability of many pathogens. Collectively, we propose that targeting of the CPSF complex, leading to widespread alternative polyadenylation of host transcripts, constitutes a general immunevasion mechanism employed by a variety of pathogenic viruses.
Identifiants
pubmed: 37582777
doi: 10.1038/s41467-023-40469-6
pii: 10.1038/s41467-023-40469-6
pmc: PMC10427651
doi:
Substances chimiques
3' Untranslated Regions
0
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4906Informations de copyright
© 2023. Springer Nature Limited.
Références
Cell. 2004 Feb 20;116(4):541-50
pubmed: 14980221
Nature. 2021 Jun;594(7862):246-252
pubmed: 33845483
Front Genet. 2022 Jan 14;12:818668
pubmed: 35096024
Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):12256-12261
pubmed: 27791013
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
Viruses. 2019 Aug 13;11(8):
pubmed: 31412613
Nature. 2018 Sep;561(7721):127-131
pubmed: 30150773
Mol Cell. 1998 Jun;1(7):991-1000
pubmed: 9651582
Mol Cell Biol. 2007 Oct;27(20):7315-33
pubmed: 17709397
NAR Genom Bioinform. 2020 Nov 21;2(4):lqaa095
pubmed: 33575639
PLoS Pathog. 2009 Sep;5(9):e1000593
pubmed: 19779565
Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):E8362-E8371
pubmed: 28928151
Biomol Concepts. 2012 Aug;3(4):345-364
pubmed: 22977648
J Virol. 2018 Mar 28;92(8):
pubmed: 29437966
Genome Biol. 2019 Oct 21;20(1):213
pubmed: 31639029
Nat Commun. 2014 Nov 20;5:5274
pubmed: 25409906
Nat Immunol. 2019 Apr;20(4):493-502
pubmed: 30833792
Nature. 2015 Jun 18;522(7556):363-7
pubmed: 25896326
Cell. 2018 Sep 6;174(6):1522-1536.e22
pubmed: 30146161
PLoS Pathog. 2013;9(10):e1003663
pubmed: 24098121
Methods Mol Biol. 2014;1169:15-25
pubmed: 24957225
J Biol Chem. 2018 Sep 21;293(38):14659-14668
pubmed: 30076219
J Gen Virol. 2008 Oct;89(Pt 10):2359-2376
pubmed: 18796704
PLoS Pathog. 2018 Mar 26;14(3):e1006954
pubmed: 29579120
J Virol. 2012 Jul;86(13):7180-91
pubmed: 22514352
J Virol. 2000 Jul;74(13):6203-6
pubmed: 10846107
Nat Rev Mol Cell Biol. 2017 Jan;18(1):18-30
pubmed: 27677860
Arch Virol. 1995;140(2):341-8
pubmed: 7710359
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Virol. 2007 Jan;81(2):514-24
pubmed: 17079289
PLoS Biol. 2007 Apr;5(4):e73
pubmed: 17355180
J Gen Virol. 2007 May;88(Pt 5):1403-1409
pubmed: 17412966
Nat Commun. 2020 Jan 15;11(1):293
pubmed: 31941886
J Virol. 2007 Jul;81(13):7011-21
pubmed: 17442719
J Virol. 2010 Dec;84(24):12761-70
pubmed: 20926573
Bioinformatics. 2019 Nov 1;35(21):4469-4471
pubmed: 30989184
Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13093-8
pubmed: 18725644
PLoS Pathog. 2019 Dec 19;15(12):e1008155
pubmed: 31856218
Virology. 1995 Dec 1;214(1):222-8
pubmed: 8525619
Virology. 2003 Mar 15;307(2):386-95
pubmed: 12667806
Am J Pathol. 2019 Dec;189(12):2389-2399
pubmed: 31585069
Nat Microbiol. 2019 Oct;4(10):1671-1679
pubmed: 31263181
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Bioorg Med Chem. 2012 Jan 1;20(1):487-97
pubmed: 22099257
Cell. 2015 Apr 23;161(3):526-540
pubmed: 25910207
Mol Cell. 2021 Feb 4;81(3):502-513.e4
pubmed: 33400923
RNA Biol. 2017 Jul 3;14(7):865-890
pubmed: 28453393
Cell Host Microbe. 2009 May 8;5(5):439-49
pubmed: 19454348
J Virol. 2010 Jul;84(14):6909-22
pubmed: 20444891
Nucleic Acids Res. 2018 Jan 4;46(D1):D1027-D1030
pubmed: 30053266
Nature. 2018 Sep;561(7722):253-257
pubmed: 30177828
J Virol. 2009 Feb;83(4):1881-91
pubmed: 19052087
Proc Natl Acad Sci U S A. 2006 May 2;103(18):7100-5
pubmed: 16627618
Virology. 1998 Dec 20;252(2):324-30
pubmed: 9878611
Cell Rep. 2018 May 15;23(7):2119-2129.e3
pubmed: 29768209
Cell Chem Biol. 2018 Dec 20;25(12):1470-1484.e5
pubmed: 30293940
Nat Commun. 2021 Dec 1;12(1):7009
pubmed: 34853303
J Exp Clin Cancer Res. 2021 Feb 1;40(1):51
pubmed: 33526057
Curr Protoc Bioinformatics. 2015 Sep 03;51:11.14.1-11.14.19
pubmed: 26334920
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nucleic Acids Res. 2019 Jul 2;47(W1):W636-W641
pubmed: 30976793
Nat Chem Biol. 2015 Jul;11(7):511-7
pubmed: 26030728
PLoS Pathog. 2018 Apr 30;14(4):e1006980
pubmed: 29709033
Am J Respir Cell Mol Biol. 2007 Mar;36(3):263-9
pubmed: 17053203
J Biol Chem. 2011 Feb 4;286(5):3681-92
pubmed: 21118815
Nat Struct Mol Biol. 2018 Sep;25(9):885-893
pubmed: 30177761
Mol Cancer Res. 2017 Sep;15(9):1206-1220
pubmed: 28584021
Adv Virus Res. 2017;97:187-243
pubmed: 28057259
PLoS Pathog. 2012;8(11):e1003059
pubmed: 23209422
Cell. 2018 Nov 29;175(6):1492-1506.e19
pubmed: 30449617
Cell. 2009 Aug 21;138(4):673-84
pubmed: 19703394
Nat Commun. 2017 Feb 24;8:14605
pubmed: 28233779
Mol Cell. 2020 Sep 17;79(6):978-990.e5
pubmed: 32857953
Science. 2014 Aug 8;345(6197):688-93
pubmed: 25104390
J Virol. 2019 Mar 21;93(7):
pubmed: 30651364
Genome Res. 2016 Aug;26(8):1145-59
pubmed: 27382025
Cell Mol Immunol. 2016 Jan;13(1):3-10
pubmed: 26189369
Virol J. 2012 Jul 28;9:139
pubmed: 22838834
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
Mol Cell. 2015 Aug 6;59(3):449-61
pubmed: 26190259
J Gen Virol. 2011 Jan;92(Pt 1):60-70
pubmed: 20881091
Curr Opin Virol. 2015 Jun;12:1-6
pubmed: 25638592
J Gen Virol. 2009 Dec;90(Pt 12):2990-2994
pubmed: 19726611
Cell Microbiol. 2007 Apr;9(4):930-8
pubmed: 17140406
Nat Commun. 2021 Aug 24;12(1):5101
pubmed: 34429411
Nat Rev Mol Cell Biol. 2022 Dec;23(12):779-796
pubmed: 35798852
Bioinformatics. 2018 Jun 1;34(11):1841-1849
pubmed: 29360928
Nat Commun. 2015 May 20;6:7126
pubmed: 25989971
Nature. 2014 Jan 2;505(7481):117-20
pubmed: 24284625