Paper ID: 301
The University of Manchester (United Kingdom)
The GTP-binding protein eIF2 acts to deliver initiator tRNA (Met-tRNAi) to the ribosome to begin protein synthesis on all cytoplasmic mRNAs. In common with other G proteins eIF2 is active when bound to GTP and not when bound to GDP. This switch enables tight control of protein synthesis. For example in times of stress global protein synthesis is repressed because Gcn2 phosphorylates eIF2α and this inhibits eIF2 activation repressing translation initiation. Stress-responsive RNAs, such as GCN4 can escape this repression. Key to controlling the activity of eIF2 are translation factors eIF2B and eIF5, thought to primarily function with eIF2-GDP and eIF2-GTP/Met-tRNAi complexes, respectively, as GEF and GAP proteins. Here I will outline work done by my lab that has identified new roles for eIF5 and eIF2B that have enabled us to develop new models for the interplay and competition between these factors for interaction with eIF2. Together these lead to either eIF2 activation or its tight control by eIF2 phosphorylation in response to stress.