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Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells
Published on: November 12, 2015
Regulation of mRNA production by the adenoviral E1B 55-kDa and E4 Orf6 proteins
1Department of Molecular Biology, Princeton University, Princeton, New Jersey 08844, USA. sjflint@molbio.princeton.edu
Abstract:
The E1B 55-kDa and E4 Orf6 proteins of human subgroup C adenoviruses both counter host cell defenses mediated by the cellular p53 protein and regulate viral late gene expression. A complex containing the two proteins has been implicated in induction of selective export of viral late mRNAs from the nucleus to the cytoplasm, with concomitant inhibition of export of the majority of newly synthesized cellular mRNAs. The molecular mechanisms by which these viral proteins subvert cellular pathways of nuclear export are not yet clear. Here, we review recent efforts to identify molecular and biochemical functions of the E1B 55-kDa and E4 Orf6 proteins required for regulation of mRNA export, the several difficulties and discrepancies that have been encountered in studies of these viral proteins, and evidence indicating that the reorganization of the infected cell nucleus and production of viral late mRNA at specific intra-nuclear sites are important determinants of selective mRNA export in infected cells. In our view, it is not yet possible to propose a coherent molecular model for regulation of mRNA export by the E1B 55-kDa and E4 Orf6 proteins. However, it should now be possible to address specific questions about the roles of potentially relevant properties of these viral proteins.
Insights
Human adenoviruses use E1B 55-kDa and E4 Orf6 proteins to control gene expression and mRNA export. These viral proteins manipulate cellular defenses, but the exact mechanisms remain unclear.
Area of Science:
- Molecular Virology
- Cell Biology
- Gene Expression Regulation
Background:
- Human subgroup C adenoviruses encode E1B 55-kDa and E4 Orf6 proteins crucial for viral replication.
- These proteins interact with and counteract host cellular p53 protein, a key regulator of cell cycle and apoptosis.
- A complex of E1B 55-kDa and E4 Orf6 proteins is known to influence mRNA export pathways.
Purpose of the Study:
- To review recent research on the molecular and biochemical functions of E1B 55-kDa and E4 Orf6 proteins in regulating mRNA export.
- To discuss challenges and discrepancies in studying these viral proteins.
- To explore the role of nuclear reorganization and viral mRNA production sites in selective mRNA export.
Main Methods:
- Literature review of studies investigating E1B 55-kDa and E4 Orf6 protein functions.
- Analysis of experimental data related to viral and cellular mRNA export.
- Discussion of biochemical and molecular mechanisms involved in subverting nuclear export pathways.
Main Results:
- Evidence suggests E1B 55-kDa and E4 Orf6 proteins induce selective export of viral late mRNAs while inhibiting cellular mRNA export.
- Nuclear reorganization and specific intra-nuclear sites for viral late mRNA production are important for this selective export.
- Despite progress, a coherent molecular model for the regulation of mRNA export by these proteins is not yet established.
Conclusions:
- The precise molecular mechanisms by which E1B 55-kDa and E4 Orf6 proteins regulate mRNA export are still under investigation.
- Future research can now focus on specific properties of these viral proteins to elucidate their roles.
- Understanding these mechanisms is vital for comprehending adenovirus pathogenesis and host-pathogen interactions.
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