VASOPRESSIN MESSENGER-RIBONUCLEIC-ACID REGULATION VIA THE PROTEIN-KINASE-A PATHWAY

Activation of vasopressin (VP) gene expression in vivo by osmotic stim uli results in an increase in both messenger RNA (mRNA) content and po lyadenylate [poly(A)] tail length. VP gene transcription in vitro is s timulated by protein kinase A (PKA) activation. To examine the role of PKA in the regulation of VP mRNA poly(A) metabolism, constructs of th e rat VP gene were permanently transfected into the mouse anterior pit uitary cell line, AtT-20. Treatment with forskolin of cells expressing the intact VP gene resulted in increased VP gene transcription, an in crease in the content of VP mRNA, and a shift toward VP mRNA species w ith longer poly(A) tails accompanied by the loss of VP mRNA species wi th shorter poly(A) tails. We uncoupled the PKA-stimulated appearance o f long-tailed species from the disappearance of short-tailed species, suggesting that the size shift was caused by a coincident, but uncoupl ed net increase in VP mRNA species with elongated poly(A) tails and ne t loss of mRNA species with short poly(A) tails. These data indicate t hat activation of the PKA second-messenger pathway both enhances trans cription of the VP gene and causes an increase in the average length o f VP mRNA poly(A) tails. This latter effect, by shifting upwards the a verage poly(A) tail size, could result in increased translational effi ciency or stability of VP mRNA, thereby providing an additional mechan ism by which PKA may enhance gene expression.