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Molecular analysis of a novel translation 'termination-reinitiation' signal

Reference	BB/C007034/1
Principal Investigator / Supervisor	Professor Ian Brierley
Co-Investigators / Co-Supervisors	Dr Thomas David Kay Brown, Professor Richard Jackson
Institution	University of Cambridge
Department	Pathology
Funding type	Research
Value (£)	208,011
Status	Completed
Type	Research Grant
Start date	01/01/2006
End date	31/12/2008
Duration	36 months

Abstract

This project will investigate the mechanism of an unconventional translational event operating in feline calicivirus. The sole sub-genomic viral RNA detected in infected cells is dicistronic, with a long 5 prime-ORF (encoding the capsid protein precursor) that overlaps a short downstream ORF by 4 nucleotides (AUGA). In virus-infected cells and in vitro systems, the downstream ORF is expressed at approximately 10-20 per cent of the level of the upstream ORF. Downstream ORF expression appears to occur by an unusual termination-reinitiation event, superficially similar to the translational coupling seen with some prokaryotic polycistronic mRNAs (e.g. ribosomal protein mRNAs), and does not seem to involve leaky scanning, shunting, IRES¿s or ribosomal frameshifting. The global objective of this project is to characterise the mechanism of expression of the downstream ORF. This will involve pursuing the following experimental objectives: mapping the segments flanking the termination-reinitiation site that are required for reinitiation; determination of the initiation factor requirements of the process; identification of protein factors that interact with the critical segment; determination of the mRNA secondary structure of this region; molecular genetic analysis of the role of structures identified in this region and of the termination and initiation codons; analysis of the effects of modulation of reinitiation efficiency on virus replication.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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