Regulation of gene expression for translation initiation factor eIF-2 alpha: importance of the 3' untranslated region

Gene expression of the alpha-subunit of eukaryotic initiation factor-2 (eIF-2 alpha), involves transcriptional and post-transcriptional mechanisms. eIF-2 alpha is a single-copy gene expressing two mRNAs, 1.6 and 4.2 kb in size. Cloning and sequencing of the cDNA for the 4.2 kb mRNA revealed that it is the result of alternative polyadenylation site selection. Four polyadenylation sites were identified within the 3' untranslated region (UTR) of eIF-2 alpha, only two of which are normally utilized in human and mouse tissues. A functional role for the extended 3' UTR was assessed by comparing the translatability and stability of the 1.6 and 4.2 kb mRNAs. Both the 1.6 and 4.2 kb transcripts could be translated in vitro and were identified in vivo as being distributed on large polyribosomes. This indicates that both mRNAs are efficiently translated. Stability studies showed that in activated T-cells the 4.2 kb mRNA was more stable than the 1.6 kb mRNA. Polyadenylation site selection and mRNA stability differ for the two mRNAs of eIF-2 alpha. These activities might be modulated by sequence elements contained within the untranslated regions of the eIF-2 alpha gene.