Evolutionary importance of translation elongation factor eEF1A variant switching: eEF1A1 down-regulation in muscle is conserved in Xenopus but is controlled at a post-transcriptional level.

Translation elongation isoform eEF1A1 has a pivotal role in protein synthesis and is almost ubiquitously expressed. In mice and rats that transcription of the gene encoding eEF1A1 is downregulated to undetectable levels in muscle after weaning; eEF1A1 is then replaced by a separately encoded but closely related isoform eEF1A2, which has only previously been described in mammals. We now show that not only is eEF1A2 conserved in non-mammalian vertebrate species, but the down-regulation of eEF1A1 protein in muscle is preserved in Xenopus, with the protein being undetectable by adulthood. Interestingly, though, this down-regulation is controlled post-transcriptionally, and levels of full-length eEF1A1 mRNA remain similar to those of eEF1A2. The switching off of eEF1A1 in muscle is therefore sufficiently important to have evolved through the use of repression operating at different levels in different species. The 3'UTR of eEF1A1 is highly conserved and contains predicted binding sites for several miRNAs, suggesting a possible method for controlling of expression. We suggest that isoform switching may have evolved because of a need for certain cell types to modify the well-established non-canonical functions of eEF1A1.