Neural expression of a novel alternatively spliced and polyadenylated Gs alpha transcript.

We have isolated an alternative transcript of the rat Gs alpha signal transduction protein gene, referred to as Gs alpha N1. Gs alpha N1 was isolated by differential hybridization screening of genes induced upon dexamethasone treatment of the neuronal-like CA77 rat thyroid C-cell line. The 1-kilobase Gs alpha N1 transcript is generated by alternative splicing and polyadenylation of a novel terminal exon. This exon lies 800 base pairs downstream of exon 3 in the Gs alpha gene. Dexamethasone differentially induced Gs alpha N1 severalfold relative to Gs alpha mRNA in the CA77 cells, similar to the bias seen with alternative processing of the calcitonin/calcitonin gene-related peptide transcript. In addition to the differential regulation by dexamethasone, the expression pattern of Gs alpha N1 in rat tissues differed markedly from Gs alpha. Gs alpha N1 mRNA was much more abundant in the brain, with intermediate levels in skeletal muscle and very low levels in other tissues. This was in contrast to the more ubiquitously expressed Gs alpha mRNA. Within the brain, Gs alpha N1 was particularly abundant in discrete regions of the brainstem and hypothalamus that modulate autonomic functions. Examination of rat embryos demonstrated that Gs alpha is expressed in both brain and nonneural tissue at least 1 day before Gs alpha N1 mRNA could be detected in the embryonic brain. Based on the regulated expression of the Gs alpha N1 transcript and previous studies on G alpha proteins, the predicted Gs alpha N1 protein may potentially modulate several heterotrimeric G protein functions in the nervous system.