Vasopressin messenger ribonucleic acid regulation via the protein kinase A pathway.
Activation of vasopressin (VP) gene expression in vivo by osmotic stimuli results in an increase in both messenger RNA (mRNA) content and polyadenylate [poly(A)] tail length. VP gene transcription in vitro is stimulated by protein kinase A (PKA) activation. To examine the role of PKA in the regulation of VP mRNA poly(A) metabolism, constructs of the rat VP gene were permanently transfected into the mouse anterior pituitary cell line, AtT-20. Treatment with forskolin of cells expressing the intact VP gene resulted in increased VP gene transcription, an increase in the content of VP mRNA, and a shift toward VP mRNA species with longer poly(A) tails accompanied by the loss of VP mRNA species with shorter poly(A) tails. We uncoupled the PKA-stimulated appearance of long-tailed species from the disappearance of short-tailed species, suggesting that the size shift was caused by a coincident, but uncoupled net increase in VP mRNA species with elongated poly(A) tails and net loss of mRNA species with short poly(A) tails. These data indicate that activation of the PKA second-messenger pathway both enhances transcription of the VP gene and causes an increase in the average length of VP mRNA poly(A) tails. This latter effect, by shifting upwards the average poly(A) tail size, could result in increased translational efficiency or stability of VP mRNA, thereby providing an additional mechanism by which PKA may enhance gene expression.
Emanuel
R L
RL
Department of Medicine, Children Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Iwasaki
Y
Y
Arbiser
Z K
ZK
Velez
E M
EM
Emerson
C H
CH
Majzoub
J A
JA
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002461:Cell Line, Transformed; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D014667:Vasopressins / Q000235:genetics*
D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014667:Vasopressins; D005576:Colforsin; D003513:Cycloheximide; D017868:Cyclic AMP-Dependent Protein Kinases