Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation.
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
12
11
2020
accepted:
09
02
2021
revised:
18
03
2021
pubmed:
9
3
2021
medline:
3
8
2021
entrez:
8
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33684133
doi: 10.1371/journal.pgen.1009263
pii: PGENETICS-D-20-01731
pmc: PMC7971895
doi:
Substances chimiques
RNA Isoforms
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009263Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM090056
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM128441
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA062203
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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