Studentship: Understanding the molecular mechanisms of cellular RNA degradation by pathogenic viruses.
Lead Research Organisation:
THE PIRBRIGHT INSTITUTE
Abstract
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Technical Summary
Studentship
:
Pathogenic viruses as parasites depend entirely on cell’s transcription machinery to express and translate their gene products necessary for a successful infection cycle. At the cellular level, this process leads to cell death; at the tissue and organ levels this process leads to loss of organ function and disease. A number of viral proteins have been shown to interfere directly with cell’s transcription machinery causing almost complete loss of cellular RNA pool. This phenomenon of loss of cellular RNA on a global scale is termed host shutoff. Paradoxically, physiological RNA turnover is also a key component of gene regulation and RNA degradation pathways play a key role in this process. Taken together, these observations imply a critical balance between physiological and pathological (virus-mediated) RNA degradation mechanisms which in turn will determine the outcome of viral infections. A recent interest in this field has been the role of RNA-binding cellular proteins which, in general, protect mRNA from cellular degradation machinery. Therefore, the aim of this project is profile these RNA-binding proteins and their associations with cellular and viral transcripts during infection with the murine ?-mmaherpesvirus-68 (MHV-68; a dsDNA virus) and with Semliki Forest Virus (SFV; an RNA virus). The key experimental approaches will include localisation of RNA-binding proteins in cells infected with MHV-68 and SFV by confocal microscopy and by polysome profiling. The latter will help identify transcripts which by-pass degradation machinery and their association with RNA-binding proteins. These approaches will help identify mechanisms by which viral transcripts may overcome degradation and at the detriment of cellular transcripts during host shutoff.
:
Pathogenic viruses as parasites depend entirely on cell’s transcription machinery to express and translate their gene products necessary for a successful infection cycle. At the cellular level, this process leads to cell death; at the tissue and organ levels this process leads to loss of organ function and disease. A number of viral proteins have been shown to interfere directly with cell’s transcription machinery causing almost complete loss of cellular RNA pool. This phenomenon of loss of cellular RNA on a global scale is termed host shutoff. Paradoxically, physiological RNA turnover is also a key component of gene regulation and RNA degradation pathways play a key role in this process. Taken together, these observations imply a critical balance between physiological and pathological (virus-mediated) RNA degradation mechanisms which in turn will determine the outcome of viral infections. A recent interest in this field has been the role of RNA-binding cellular proteins which, in general, protect mRNA from cellular degradation machinery. Therefore, the aim of this project is profile these RNA-binding proteins and their associations with cellular and viral transcripts during infection with the murine ?-mmaherpesvirus-68 (MHV-68; a dsDNA virus) and with Semliki Forest Virus (SFV; an RNA virus). The key experimental approaches will include localisation of RNA-binding proteins in cells infected with MHV-68 and SFV by confocal microscopy and by polysome profiling. The latter will help identify transcripts which by-pass degradation machinery and their association with RNA-binding proteins. These approaches will help identify mechanisms by which viral transcripts may overcome degradation and at the detriment of cellular transcripts during host shutoff.
Planned Impact
unavailable