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• W2950557029 endingPage "e1007884" @default.
• W2950557029 startingPage "e1007884" @default.
• W2950557029 abstract "In contrast to human cells, very few HSV-1 genes are known to be spliced, although the same pre-mRNA processing machinery is shared. Here, through global analysis of splice junctions in cells infected with HSV-1 and an HSV-1 mutant virus with deletion of infectious cell culture protein 27 (ICP27), one of two viral immediate early (IE) genes essential for viral replication, we identify hundreds of novel alternative splice junctions mapping to both previously known HSV-1 spliced genes and previously unknown spliced genes, the majority of which alter the coding potential of viral genes. Quantitative and qualitative splicing efficiency analysis of these novel alternatively spliced genes based on RNA-Seq and RT-PCR reveals that splicing at these novel splice sites is efficient only when ICP27 is absent; while in wildtype HSV-1 infected cells, the splicing of these novel splice junctions is largely silenced in a gene/sequence specific manner, suggesting that ICP27 not only promotes accumulation of ICP27 targeted transcripts but also ensures correctness of the functional coding sequences through inhibition of alternative splicing. Furthermore, ICP27 toggles expression of ICP34.5, the major viral neurovirulence factor, through inhibition of splicing and activation of a proximal polyadenylation signal (PAS) in the newly identified intron, revealing a novel regulatory mechanism for expression of a viral gene. Thus, through the viral IE protein ICP27, HSV-1 co-opts both splicing and polyadenylation machinery to achieve optimal viral gene expression during lytic infection. On the other hand, during latent infection when ICP27 is absent, HSV-1 likely takes advantages of host splicing machinery to restrict expression of randomly activated antigenic viral genes to achieve immune evasion." @default.
• W2950557029 created "2019-06-27" @default.
• W2950557029 creator A5043844258 @default.
• W2950557029 creator A5049156843 @default.
• W2950557029 creator A5057743088 @default.
• W2950557029 date "2019-06-17" @default.
• W2950557029 modified "2023-10-05" @default.
• W2950557029 title "Hidden regulation of herpes simplex virus 1 pre-mRNA splicing and polyadenylation by virally encoded immediate early gene ICP27" @default.
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• W2950557029 doi "https://doi.org/10.1371/journal.ppat.1007884" @default.
• W2950557029 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6597130" @default.
• W2950557029 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31206552" @default.
• W2950557029 hasPublicationYear "2019" @default.
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