Translational regulation of Na-K-ATPase subunit mRNAs by glucocorticoids

Glucocorticoids (GC) regulate Na-K-ATPase-subunit mRNA transcription. However, GC-induced increases in Na-K-ATPase activity are not always paralleled by changes in subunit mRNA abundance. We therefore examined posttranscriptional mechanisms of subunit gene regulation by GC. cDNA-derived mRNAs encoding alpha1-, alpha3-, and beta1-subunits were tested for stability and translation efficiency in a cell-free lysate, in the presence of hydrocortisone (HC) or dexamethasone (Dex). No effect of HC on subunit mRNA stability was noted. Translation efficiency of alpha1- and alpha3- mRNAs, but not of beta1-mRNA, was significantly increased by HC and Dex. Deletion of the 5' untranslated region (5'UT) of alpha1- mRNA abolished this effect. Translation of a chimeric beta1-mRNA, constructed by transposing the 5'UT of alpha1 onto the coding region of beta1, was enhanced by HC. Transposition of a putative steroid-modulatory element conserved in the 5'UT of all alpha isoforms (ACAGGACCC) onto the coding region of beta1-mRNA rendered it responsive to HC. A synthetic primer containing the ACAGGACCC sequence abolished the effect of HC on alpha1- and chimeric beta1-mRNAs. Our results indicate that GC can directly enhance Na-K-ATPase translation in vitro in a subunit-specific manner, via a putative GC-modulatory element situated in a predicted loop structure within the 5'UT of alpha -mRNAs.