Professor Catherine Abbott, School of Molecular Genetic and Population Health Sciences, University of Edinburgh
Monday 9th December 2013, 4.00 p.m., Ingram Lecture Theatre
eEF1A2 is a translation elongation factor that plays a pivotal role in protein synthesis in neurons and muscle. eEF1A is unusual in that two independently encoded isoforms with distinct tissue-specific expression patterns are found throughout vertebrate evolution; whereas eEF1A1 is expressed in all tissues throughout development, it is downregulated postnatally to undetectable levels in muscle and neurons whilst remaining at high levels in all other tissues. In muscle (skeletal and cardiac) and neurons eEF1A1 is replaced by eEF1A2, which is 92% identical and 98% similar to eEF1A1. The question of why this very specific change from one eEF1A isoform to another occurs, and the functional consequences of the switch, is of fundamental biological importance. Deletion of eEF1A2 in mice gives rise to a severe motor neuron degeneration phenotype; conversely, eEF1A2 is oncogenic when inappropriately expressed in tissues that normally express eEF1A1 only. We use comparative homology modelling, cellular assays and transgenic mice to study the roles of the two isoforms in health and disease.