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Herpesvirus mRNAs are sorted for export via Crm1-dependent and -independent pathways
1Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Abstract:
Cellular pre-mRNA splicing is inhibited by ICP27, a herpes simplex virus regulatory protein, resulting in the shutoff of host protein synthesis. Here we reveal that ICP27 also mediates the export of some virus RNAs via a Crm1-dependent pathway and present evidence that independent domains are required for these functions. Sorting of some viral mRNAs for nuclear export requires Crm1, while other virus mRNAs are exported via another pathway.
Insights
Herpes simplex virus ICP27 protein inhibits cellular splicing and host protein synthesis. ICP27 also exports viral RNAs through a Crm1-dependent pathway, requiring distinct protein domains.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- Herpes simplex virus (HSV) ICP27 is a key regulatory protein.
- ICP27 is known to inhibit cellular pre-mRNA splicing.
- This inhibition leads to the shutoff of host protein synthesis during viral infection.
Purpose of the Study:
- To investigate the role of ICP27 in viral RNA export.
- To determine if ICP27 utilizes specific cellular pathways for RNA export.
- To identify distinct functional domains within ICP27 responsible for splicing inhibition and RNA export.
Main Methods:
- Analysis of viral RNA localization and export pathways.
- Investigation of the Crm1-dependent export pathway.
- Functional domain mapping of ICP27.
Main Results:
- ICP27 mediates the nuclear export of certain viral RNAs.
- This export process is dependent on the Crm1 pathway.
- Evidence suggests that separate domains of ICP27 are responsible for splicing inhibition and RNA export functions.
- Different viral mRNAs utilize distinct pathways for nuclear export.
Conclusions:
- ICP27 plays a dual role in viral infection: inhibiting host splicing and facilitating viral RNA export.
- The Crm1 pathway is essential for the export of some viral RNAs mediated by ICP27.
- ICP27 possesses distinct functional domains, highlighting the complexity of its regulatory mechanisms in herpes simplex virus replication.