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| Content Provider | PubMed Central |
|---|---|
| Author | Shu, Minfeng Taddeo, Brunella Roizman, Bernard |
| Editor | Sandri-goldin, R. M. |
| Copyright Year | 2015 |
| Abstract | Herpes simplex viruses (HSV) package and bring into cells an RNase designated virion host shutoff (VHS) RNase. In infected cells, the VHS RNase targets primarily stress response mRNAs characterized by the presence of AU-rich elements in their 3′ untranslated regions (UTRs). In uninfected cells, these RNAs are sequestered in exosomes or P bodies by host proteins that bind to the AU-rich elements. In infected cells, the AU-rich RNAs are deadenylated and cleaved close to the AU-rich elements, leading to long-term persistence of nontranslatable RNAs consisting of the 5′ portions of the cleavage products. The host proteins that bind to the AU-rich elements are either resident in cells (e.g., TIA-1) or induced (e.g., tristetraprolin). Earlier, this laboratory reported that tristetraprolin binds VHS RNase. To test the hypothesis that tristetraprolin directs VHS RNase to the AU-rich elements, we mapped the domains of VHS and tristetraprolin required for their interactions. We report that VHS binds to the domain of tristetraprolin that enables its interaction with RNA. A single amino acid substitution in that domain abolished the interaction with RNA but did not block the binding to VHS RNase. In transfected cells, the mutant but not the wild-type tristetraprolin precluded the degradation of the AU-rich RNAs by VHS RNase. We conclude that TTP mediates the cleavage of the 3′ UTRs of stress response mRNAs by recruiting the VHS RNase to the AU-rich elements. |
| Related Links | http://dx.doi.org/10.1128/jvi.00091-15 |
| Ending Page | 5650 |
| Page Count | 8 |
| Starting Page | 5643 |
| File Format | |
| ISSN | 0022538X |
| e-ISSN | 10985514 |
| Journal | Journal of Virology |
| Issue Number | 10 |
| Volume Number | 89 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2015-05-15 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Immunology Virology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Virology Immunology Microbiology Insect Science |
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