On the Need to Tell Apart Fraternal Twins eEF1A1 and eEF1A2, and Their Respective Outfits

Abstract

eEF1A1 and eEF1A2 are paralogous proteins whose presence in most normal eukaryotic cells is mutually exclusive and developmentally regulated. Often described in the scientific literature under the collective name eEF1A, which stands for eukaryotic elongation factor 1A, their best known activity (in a monomeric, GTP-bound conformation) is to bind aminoacyl-tRNAs and deliver them to the A-site of the 80S ribosome. However, both eEF1A1 and eEF1A2 are endowed with multitasking abilities (sometimes performed by homo- and heterodimers) and can be located in different subcellular compartments, from the plasma membrane to the nucleus. Given the high sequence identity of these two sister proteins and the large number of post-translational modifications they can undergo, we are often confronted with the dilemma of discerning which is the particular proteoform that is actually responsible for the ascribed biochemical or cellular effects. We argue in this review that acquiring this knowledge is essential to help clarify, in molecular and structural terms, the mechanistic involvement of these two ancestral and abundant G proteins in a variety of fundamental cellular processes other than translation elongation. Of particular importance for this special issue is the fact that several de novo heterozygous missense mutations in the human EEF1A2 gene are associated with a subset of rare but severe neurological syndromes and cardiomyopathies.

Analysis of the Expression and Subcellular Distribution of eEF1A1 and eEF1A2 mRNAs during Neurodevelopment

“…It was unexpected to find that mature hippocampal neurons coexpress eEF1A1 and eEF1A2 mRNAs in in vitro cultured neurons and tissue samples obtained from 90-week-old mice ( Figure 2 , Figure 3 , Figure 5 and Figure S1 ). It is well accepted that the expression of these two paralogue genes is mutually exclusive in adult cells, and only cancer cells express them simultaneously [ 9 , 18 , 80 , 81 ]. We should consider that eEF1A1 mRNAs might be translationally repressed, which would explain the discrepancy between our results and those of previous studies using antibodies.…”

“…Both eEF1A variants are endowed with the capacity to coordinate changes in local protein synthesis and cytoskeleton reorganization in neurons. Therefore, they sustain the functional development of the brain [ 17 , 18 , 19 , 20 ]. The canonical role of both eEF1A1 and eEF1A2 in translation elongation is to bring aminoacyl transfer RNAs (tRNAs) to the A site of the 80S ribosome in a GTP-dependent manner [ 8 , 11 , 21 , 22 ].…”

Initiation and elongation factor co-expression correlates with recurrence and survival in epithelial ovarian cancer

“…eEF1A1 is involved in the regulation of the cytoskeleton and also in the control of cell proliferation and death [ 43 ]. Interestingly, it has been reported, that the presence of eEF1A1 and eEF1A2 in most normal cells is mutually exclusive [ 44 ]. Improved understanding on how the relation of eEF1A1 towards eEF1A2 in OC is will offer us also better abilities to use this marker, which showed significant correlation with OS, for prognostic purposes.…”

Glycosylating Effectors of Legionella pneumophila: Finding the Sweet Spots for Host Cell Subversion

“…This underlines the critical nature of this residue and suggests that reversible serine-53 phosphorylation might dynamically control the pool of eEF1A available for protein synthesis in uninfected cells. Moreover, an increasing number of post-translational modifications on eEF1A, directing its involvement in various processes beyond translation, is reported [ 72 , 73 , 74 , 75 ]. Intriguingly, phosphorylation of serine-53 was proposed to enhance the interaction of eEF1A with phosphatidylinositol (PI) 4-kinase (PI4K) IIIβ, leading to activation of the PI4K [ 73 ].…”