Neural expression of a novel alternatively spliced and polyadenylated Gsα transcript

Abstract

We have isolated an alternative transcript of the rat Gsα signal transduction protein gene, referred to as GsαN1. GsαN1 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 GsαN1 transcript is generated by alternative splicing and polyadenylation of a novel terminal exon. This exon lies 800 base pairs down-stream of exon 3 in the Gsα gene. Dexamethasone differentially induced GsαN1 severalfold relative to Gsα 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 GsαN1 in rat tissues differed markedly from Gsα. GsαN1 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 Gsa mRNA. Within the brain, GsαN1 was particularly abundant in discrete regions of the brainstem and hypothalamus that modulate autonomic functions. Examination of rat embryos demonstrated that Gsa is expressed in both brain and nonneural tissue at least 1 day before GsαN1 mRNA could be detected in the embryonic brain. Based on the regulated expression of the GsαN1 transcript and previous studies on Ga proteins, the predicted GsαN1 protein may potentially modulate several heterotrimeric G protein functions in the nervous system.