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Publications of the Week

Targeting Nup358/RanBP2 by a Viral Protein Disrupts Stress Granule Formation

By January 4, 2023February 23rd, 2023No Comments

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This week we profile a recent publication in PLOS Pathogens from Dr. Jibin Sadasivan (pictured, left) and a team in Dr. Eric Jan’s (right) lab at UBC.

Can you provide a brief overview of your lab’s current research focus?

The overarching theme of our lab is to investigate the virus-host interactions during RNA virus infections. This includes key steps in the viral life cycle such as host ribosome hijacking by the viral RNA and viral proteins that modulate host cellular processes and evade host antiviral responses to promote infection. Using a wide range of molecular and biochemical approaches, we investigate fundamental questions on RNA virus infection to the use of viral mechanisms for therapeutic applications. 

Read more about our research here.

What is the significance of the findings in this publication?

Cells have the remarkable ability to respond to stress. During stress conditions, the RNA and proteins in the cytoplasm, assemble and form granular structures called stress granules. The mechanism and consequence of stress granule formation are not well understood. However, defects in SG formation are associated with many diseases such as neurodegenerative diseases and cancer. Moreover, viruses often inhibit stress granule formation. How this occurs and why this would benefit virus infection is not known. In this study, we unraveled a novel mechanism by which a multifunctional viral protein modulates nuclear processes such as mRNA export and transcription to regulate stress granule formation. The viral protein targets a nuclear pore protein to block the export of RNA, that are required for stress granule formation in cytoplasm. We identified a unique stress granule regulation mechanism, exploited by a virus, that can potentially be targeted to control disease-associated stress granules. 

What are the next steps for this research?

This study in combination with our ongoing studies opens up many new areas for our research. We are keen to uncover the identity of specific RNAs that are accumulated in the nucleus and investigate their role in stress granule formation. This would provide a global picture of stress granule formation. We are also exploring the possibility of utilizing the viral protein as a research/therapeutic tool to block and uncouple stress granule functions that are associated with neurodegenerative diseases such as ALS.

If you’d like to mention your funding sources, please list them.

Our work was supported by Canadian Institute of Health Research operating grant (PJT-178342) to Eric Jan; Natural Sciences and Engineering Research Council of Canada Discovery grant (RGPIN-2017-04515) to Eric Jan; National Institutes of Health (A132131 – R01AI137471)  to Raul Andino and SERB-UBC Doctoral scholarship to Jibin Sadasivan.

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