Understanding functions of eEF1 translation elongation factors beyond translation. A proteomic approach.

Mammalian translation elongation factors eEF1A1 and eEF1A2 are 92% homologous isoforms whose mutually exclusive tissue-specific expression is regulated during development. The isoforms have similar translation functionality, but show differences in spatial organization and participation in various processes, such as oncogenesis and virus reproduction. The differences may be due to their ability to interact with isoform-specific partner proteins. We used the identified sets of eEF1A1 or eEF1A2 partner proteins to identify cell complexes and/or processes specific to one particular isoform. As a result, we found isoform-specific interactions reflecting the involvement of different eEF1A isoforms in different cellular processes, including actin-related, chromatin-remodeling, ribonuclease H2, adenylyl cyclase, and Cul3-RING ubiquitin ligase complexes as well as initiation of mitochondrial transcription. An essential by-product of our analysis is the elucidation of a number of cellular processes beyond protein biosynthesis, where both isoforms appear to participate such as large ribosomal subunit biogenesis, mRNA splicing, DNA mismatch repair, 26S proteasome activity, P-body and exosomes formation, protein targeting to the membrane. This information suggests that a relatively high content of eEF1A in the cell may be necessary not only to maintain efficient translation, but also to ensure its participation in various cellular processes, where some roles of eEF1A have not yet been described. We believe that the data presented here will be useful for deciphering new auxiliary functions of eEF1A and its isoforms, and provide a new look at the known non-canonical functions of this main component of the human translation-elongation machinery.