Inappropriate expression of the translation elongation factor 1A disrupts genome stability and metabolism

Abstract

The translation elongation factor eEF1A is one of the most abundant proteins found within cells and its role within protein synthesis is well documented. Levels of eEF1A are tightly controlled, with inappropriate expression linked to oncogenesis. However the mechanisms by which increased eEF1A expression alter cell behaviour are unknown. Our analyses in yeast suggest that elevation of eEF1A levels lead to stabilisation of the spindle pole body and changes in nuclear organisation. Elevation of eEF1A2 also leads to altered nuclear morphology in cultured human cells suggesting a conserved role in maintaining genome stability. Gene expression and metabolomic analyses reveal that the level of eEF1A is crucial for the maintenance of metabolism and amino acid levels in yeast, most likely via its role in the control of vacuole function. Increased eEF1A2 levels trigger lysosome biogenesis in cultured human cells, also suggesting a conserved role within metabolic control mechanisms. Together our data suggest that the control of eEF1A levels is important for the maintenance of a number of cell functions out-with translation, whose de-regulation may contribute to its oncogenic properties.