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In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
Published on: January 29, 2018
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Epstein-Barr virus encoded microRNAs target SUMO-regulated cellular functions.
Simone Callegari1, Stefano Gastaldello, Omid R Faridani
1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
The FEBS Journal
|September 11, 2014
Summary
Epstein-Barr virus microRNAs target the SUMOylation network, impacting cellular stress and immune responses. Viral miRNAs inhibit key pathways like TGF-beta, affecting viral replication and pathogenesis.
Area of Science:
- Molecular Biology
- Virology
- Cellular Biology
Background:
- Post-translational modification by SUMOylation regulates cellular stress responses and viral infections.
- Epstein-Barr virus (EBV) encodes microRNAs (miRNAs) with poorly understood functions.
- Understanding viral miRNA interactions with host cell machinery is crucial for pathogenesis research.
Purpose of the Study:
- To investigate the interference of EBV-encoded miRNAs with the SUMOylation signaling network.
- To identify host SUMO interactome members targeted by EBV miRNAs.
- To elucidate the functional consequences of this interference on cellular processes and viral replication.
Main Methods:
- Computational analysis of miRNA-mRNA target pairs to predict SUMO interactome members targeted by EBV miRNAs.
- Functional network analysis of predicted target genes.
- Experimental validation using lentiviral transduction and productive viral cycle induction.
- Assessing the impact of BHRF1 miRNAs on TGF-beta signaling pathway components.
Main Results:
- Identified 575 potential SUMO interactome targets of EBV miRNAs.
- Predicted targets are enriched in functional networks controlling chromatin organization, stress, DNA damage, immune responses, apoptosis, and TGF-beta signaling.
- Upregulation of BHRF1 miRNAs inhibited multiple components of the TGF-beta signaling pathway.
Conclusions:
- EBV miRNAs can effectively interfere with SUMO-regulated cellular functions.
- This interference impacts critical cellular processes involved in viral replication and pathogenesis.
- Viral miRNAs represent a significant mechanism by which EBV manipulates host cell pathways.
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