Investigation of the obligatory coupling of bunyavirus transcription to ribosome translocation. (360G-Wellcome-084332_Z_07_Z)

£237,491

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