Translation Elongation Factor eEF1A2 Is Essential for Post-weaning Survival in Mice

Abstract

Translation elongation factor eEF1A, formerly known as EF-1␣, exists as two variant forms; eEF1A1, which is almost ubiquitously expressed, and eEF1A2, whose expression is restricted to muscle and brain at the level of whole tissues. Expression analysis of these genes has been complicated by a general lack of availability of antibodies that specifically recognize each variant form. Wasted mice (wst/wst) have a 15.8-kilobase deletion that abolishes activity of eEF1A2, but before this study it was unknown whether the deletion also affected neighboring genes. We have generated a panel of anti-peptide antibodies and used them to show that eEF1A2 is expressed at high levels in specific cell types in tissues previously thought not to express this variant, such as pancreatic islet cells and enteroendocrine cells in colon crypts. Expression of eEF1A1 and eEF1A2 is shown to be generally mutually exclusive, and we relate the expression pattern of eEF1A2 to the phenotype seen in wasted mice. We then carried out a series of transgenic experiments to establish whether the expression of other genes is affected by the deletion in wasted mice. We show that aspects of the phenotype such as motor neuron degeneration relate precisely to the relative expression of eEF1A1 and eEF1A2, whereas the immune system abnormalities are likely to result from a stress response. We conclude that loss of eEF1A2 function is solely responsible for the abnormalities seen in these mice.

eEF1A Phosphorylation in the Nucleus of Insulin-stimulated C2C12 Myoblasts

“…In recent years, two lines of evidence have implicated eEF1A2 in disease, suggesting that there may indeed be subtle differences in the functions of the two forms of eEF1A. First, EEF1A2 has been shown to be a potential oncogene; it is overexpressed in a proportion of ovarian tumors but is not expressed in normal ovary (51), and it is similarly overexpressed in two-thirds of breast tumors but not normal breast tissue (52,53). Phosphorylation has been determined to modify some of the activities of mammalian eEF1A, typically resulting in a stimulatory effect (32,54).…”

Translation elongation factor-1A1 (eEF1A1) localizes to the spine by domain III

“…eEF1A1 is almost ubiquitously expressed, while eEF1A2 is normally expressed only in the heart, muscles, brain (13)(14)(15)(16), pancreatic islet cells, and enteroendocrine cells in colon crypts (16). During postnatal development, a transition from eEF1A1 to eEF1A2 occurs.…”

Raf kinases in signal transduction and interaction with translation machinery

“…The near-ubiquitous form, eEF1A1, is expressed in all tissues throughout development but is absent in adult muscle and heart, which express eEF1A2 instead (68,69) . eEF1A2 is also found in some other cell types, including large motor neurons, islet cells in the pancreas and enteroendocrine cells in the gut (70,71) . We showed that in H1355, treatment with IFN α increased both eEF1A1 and eEF1A2 expression, but to different degrees and with different kinetics.…”