Journal
EMBO JOURNAL
Volume 22, Issue 7, Pages 1608-1619Publisher
WILEY
DOI: 10.1093/emboj/cdg166
Keywords
HSV-1; ICP27; splicing; SRPK1; SR protein phosphorylation
Categories
Funding
- NIAID NIH HHS [R37 AI021515, R01 AI021515, T32-AI-07319, AI21515, T32 AI007319] Funding Source: Medline
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Infection with some viruses can alter cellular mRNA processing to favor viral gene expression. We present evidence that herpes simplex virus 1 (HSV-1) protein ICP27, which contributes to host shut-off by inhibiting pre-mRNA splicing, interacts with essential splicing factors termed SR proteins and affects their phosphorylation. During HSV-1 infection, phosphorylation of several SR proteins was reduced and this correlated with a subnuclear redistribution. Exogenous SR proteins restored splicing in ICP27-inhibited nuclear extracts and SR proteins isolated from HSV-1-infected cells activated splicing in uninfected S100 extracts, indicating that inhibition occurs by a reversible mechanism. Spliceosome assembly was blocked at the pre-spliceosomal complex A stage. Furthermore, we show that ICP27 interacts with SRPK1 and relocalizes it to the nucleus; moreover, SRPK1 activity was altered in the presence of ICP27 in vitro. We propose that ICP27 modifies SRPK1 activity resulting in hypophosphorylation of SR proteins impairing their ability to function in spliceosome assembly.
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