eIF2A regulates cell migration in a translation-independent manner

The RNA-binding protein eukaryotic translation initiation factor 2A (eIF2A) is an alternative translation initiation factor shown to drive tumor formation by facilitating translation from near-cognate initiation codons. Here, we uncover a function for eIF2A in regulating cell migration in a manner independent of overt control of translation. Using a melanoma cell model consisting of nontumoral melanocytic Mel-ST cells and their metastatic counterpart obtained by H-Ras transformation, we unexpectedly find minimal effects of eIF2A depletion on translation. Interactome studies identified centrosomal proteins as major binding partners of eIF2A. We found that eIF2A colocalizes with the centrosome, enhances centrosome composition, and promotes centrosome orientation during cell migration. Migration requires the C-terminal disordered region of eIF2A, involved in mRNA binding. Interaction with mRNA, however, does not require ongoing translation. These findings reveal a role for eIF2A in centrosome dynamics beyond its traditional function in translation.