XB-ART-43482Biochem Biophys Res Commun. July 22, 2011; 411 (1): 19-24.
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.
PubMed ID: 21722626
Article link: Biochem Biophys Res Commun.
Grant support: 5T32 GM07464 NIGMS NIH HHS , MC_U117560482 Medical Research Council , 8983 Cancer Research UK, CRUK_8983 Cancer Research UK, MRC_MC_U117560482 Medical Research Council
Genes referenced: eef1a1 eef1a2 rpl8
Antibodies referenced: Eef1a2 Ab1
Article Images: [+] show captions
|Fig. 1. Figure 1 shows the results of ClustalW analysis of eEF1A1 and eEF1A2 from X. laevis, X. tropicalis and mouse; the results were coloured using Boxshade. Xt is X. tropicalis, Xl is X. laevis, m is mouse; 1A1 is eEF1A1, 1A2 is eEF1A2. An asterisk denotes the position of the serine residue present in eEF1A2 from all species that is predicted to be a phosphorylation site.|
|Fig. 2. Panel A: RT-PCR of eEF1A1 (top panel) and eEF1A2 (bottom panel) in RNA from a range of tissues taken from adult X. laevis. Li = liver, Lu = lung, S = spleen, O = oocytes, G = gall bladder, B = brain, H = heart, M = muscle (two independent tissue samples). No-RT controls were carried out and were negative for all tissues for both genes (data not shown). Panel B: Western blots of eEF1A1 (top) and eEF1A2 (bottom). Gels were run in duplicate using the samples of same protein extract at the same time. Og = optic ganglion, B = brain, Sc = spinal cord, M = muscle, Li = liver, G = gall bladder, Lu = lung, K = kidney, S = spleen. Panel C: Immunohistochemistry for eEF1A2 on spinal cord and cardiac muscle from X. laevis, together with negative controls. eEF1A2 shows widespread expression in cardiac muscle but is expressed in only in neuronal cells in spinal cord.|