NEURAL EXPRESSION OF A NOVEL ALTERNATIVELY SPLICED AND POLYADENYLATEDGS-ALPHA TRANSCRIPT

We have isolated an alternative transcript of the rat Gsalpha signal t ransduction protein gene, referred to as GsalphaN1. GsalphaN1 was isol ated by differential hybridization screening of genes induced upon dex amethasone treatment of the neuronal-like CA77 rat thyroid C-cell line . The 1-kilobase GsalphaN1 transcript is generated by alternative spli cing and polyadenylation of a novel terminal exon. This exon lies 800 base pairs downstream of exon 3 in the Gsalpha gene. Dexamethasone dif ferentially induced GsalphaN1 severalfold relative to Gsalpha mRNA in the CA77 cells, similar to the bias seen with alternative processing o f the calcitonin/calcitonin gene-related peptide transcript. In additi on to the differential regulation by dexamethasone, the expression pat tern of GsalphaN1 in rat tissues differed markedly from Gsalpha. Gsalp haN1 mRNA was much more abundant in the brain, with intermediate level s in skeletal muscle and very low levels in other tissues. This was in contrast to the more ubiquitously expressed Gsalpha mRNA. Within the brain, GsalphaN1 was particularly abundant in discrete regions of the brainstem and hypothalamus that modulate autonomic functions. Examinat ion of rat embryos demonstrated that Gsalpha is expressed in both brai n and nonneural tissue at least 1 day before GsalphaN1 mRNA could be d etected in the embryonic brain. Based on the regulated expression of t he GsalphaN1 transcript and previous studies on Galpha proteins, the p redicted GsalphaN1 protein may potentially modulate several heterotrim eric G protein functions in the nervous system.