Investigation of the obligatory coupling of bunyavirus transcription to ribosome translocation. (360G-Wellcome-084332_Z_07_Z)
Bunyaviruses are unique among negative-strand RNA viruses in that their transcription is obligatorily coupled to translation. We recently showed this coupling was because ribosomes must translocate along nascent mRNAs as they are transcribed. When translation is prevented, the bunyavirus RNA-dependant RNA polymerase (RdRp) prematurely terminates transcription, causing a fatal-loss of gene expression. The aim of this proposal is to determine how ribosomes affect RdRp activity. Experimental eviden ce favors two models: The first proposes that ribosomes prevent termination by colliding with RdRps paused at termination sites. This model will be tested by preventing this collision, achieved by both slowing-down ribosome translocation, and also by increasing the distance between the point of ribosome assembly and the site of termination. The second model proposes that ribosomes prevent termination by disrupting RNA interactions specified by the termination signal that are required for its act ivity. We will test this possibility by performing a comprehensive functional analysis of the bunyavirus termination signal, to determine whether formation of RNA interactions determines termination signaling ability. In addition, host cell factors are known to promote the RdRp-ribosome interaction. We will attempt to identify these components to further reveal molecular details of how the ribosome affects RdRp activity.
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Grant Details
Amount Awarded | 237491 |
Applicant Surname | Barr |
Approval Committee | Immunology and Infectious Disease Funding Committee |
Award Date | 2008-02-07T00:00:00+00:00 |
Financial Year | 2007/08 |
Grant Programme: Title | Project Grant |
Internal ID | 084332/Z/07/Z |
Lead Applicant | Dr John Barr |
Partnership Value | 237491 |
Planned Dates: End Date | 2012-03-31T00:00:00+00:00 |
Planned Dates: Start Date | 2008-03-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Yorkshire and the Humber |