Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation.
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Authors
Wang, XiuyeLiu, Liang
Whisnant, Adam W
Hennig, Thomas
Djakovic, Lara
Haque, Nabila
Bach, Cindy
Sandri-Goldin, Rozanne M
Erhard, Florian
Friedel, Caroline C
Dölken, Lars
Shi, Yongsheng
Issue Date
2021-03-08
Metadata
Show full item recordAbstract
Eukaryotic gene expression is extensively regulated by cellular stress and pathogen infections. We have previously shown that herpes simplex virus 1 (HSV-1) and several cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes and that the viral immediate early factor ICP27 plays an important role in HSV-1-induced DoTT. Here, we show that HSV-1 infection also leads to widespread changes in alternative polyadenylation (APA) of host mRNAs. In the majority of cases, polyadenylation shifts to upstream poly(A) sites (PAS), including many intronic PAS. Mechanistically, ICP27 contributes to HSV-1-mediated APA regulation. HSV-1- and ICP27-induced activation of intronic PAS is sequence-dependent and does not involve general inhibition of U1 snRNP. HSV1-induced intronic polyadenylation is accompanied by early termination of RNAPII. HSV-1-induced mRNAs polyadenylated at intronic PAS (IPA) are exported into the cytoplasm while APA isoforms with extended 3' UTRs are sequestered in the nuclei, both preventing the expression of the full-length gene products. Finally we provide evidence that HSV-induced IPA isoforms are translated. Together with other recent studies, our results suggest that viral infection and cellular stresses induce a multi-faceted host response that includes DoTT and changes in APA profiles.Citation
PLoS Genet. 2021 Mar 8;17(3):e1009263. doi: 10.1371/journal.pgen.1009263.Affiliation
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.Publisher
PLOSJournal
PLoS geneticsPubMed ID
33684133Type
ArticleLanguage
enEISSN
1553-7404ae974a485f413a2113503eed53cd6c53
10.1371/journal.pgen.1009263
Scopus Count
The following license files are associated with this item:
- Creative Commons
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