eIF2A represses cell wall biogenesis gene expression in Saccharomyces cerevisiae. undefined

Translation initiation is a complex and highly regulated process that represents an important mechanism, controlling gene expression. eIF2A was proposed to work as an alternative initiation factor, but its role is unclear, and its biological targets remain to be discovered. To gain insight into the function of eIF2A in Saccharomyces cerevisiae, we identified mRNAs associated with the eIF2A complex and showed that 24% of the most enriched mRNAs encode proteins related to cell wall biogenesis and maintenance. In agreement with this result, we showed that eIF2A deletion sensitizes cells to cell wall damage induced by calcofluor white. eIF2A overexpression led to a growth defect, correlated with a decrease of the expression of several cell wall proteins. In contrast, none changes were observed in the transcriptome, suggesting that eIF2A controls the expression of the cell wall-related proteins at a translational level. The biochemical characterization of the eIF2A complex revealed that eIF2A strongly interacts with the RNA binding protein Ssd1, which is a negative translational regulator, controlling the expression of cell wall-related genes. Interestingly, eIF2A and Ssd1 bound several common mRNA targets and we found that the binding of eIF2A to some targets was mediated by Ssd1. Surprisingly, we further showed that eIF2A is physically and functionally associated with the exonuclease Xrn1 and other mRNA degradation factors, suggesting an additional level of regulation. Altogether, our results highlight new aspects of the complex and redundant fine-tuned regulation of proteins expression related to the cell wall, a structure required to maintain cell shape and rigidity providing protection against harmful environmental stresses.