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Role of translation initiation factor eF1-2 in cap-dependent and cap-independent (internal) initiation of protein synthesis

Reference	BBS/E/I/00000190
Principal Investigator / Supervisor	Professor Graham Belsham
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	30,864
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	30/09/1998
Duration	18 months

Abstract

Translation initiation factor eIF2 forms a ternary complex with met-tRNA and GTP and plays a critical role in the initiation step of protein synthesis. The protein comprises three subunits. Phosphorylation of the alpha subunit blocks eIF2 recycling and inhibits protein synthesis. The beta- subunit of the complex has been shown to bind to picornavirus internal ribosome entry site (IRES) elements and to affect the selection of the initiation codon in yeast and mammalian systems. The project is intended to further our understanding of the role of this initiation factor in both cap-dependent and cap-independent protein synthesis, the latter directed by picornavirus internal ribosome entry site (IRES) elements. The role of the three subunits in the activities of this protein will be characterised through structure-function analyses. The role of this protein in the site selection mechanism of protein synthesis is of particular relevance to foot-and-mouth disease virus since initiation of protein synthesis occurs at two distinct sites. The inhibition of eIF2 activity is a common defence response to virus infection and thus viruses often employ specific mechanisms to overcome this. Thus the regulation of this protein is a key area of virus-host interaction. Enabling technologies: Methods are being developed for the specific depletion of eIF2 from translation extracts which may prove useful in other contexts within the Institute. The structural analysis of a portion of the beta subunit using NMR should increase our knowledge of RNA/protein interactions and enhance familiarity with this technology which will promote further applications when appropriate. Understanding: At this early stage of the project, progress to date is necessarily limited but includes successful depletion of eIF2 and reconstitution of translation activity by addition of exogeneous eIF2 which should allow studies to proceed. A structure- function analysis of protein/RNA interactions should have relevance to many systems and may direct other analyses. Characterisation of depletion technologies may be useful in designing strategies to manipulate biochemical pathways within organisms.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
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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