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Chunk #28 — NOVEL IMPRINTED GENE PRODUCTS OF THE GNAS LOCUS — The A/B Transcript

Source
The GNAS Locus: Quintessential Complex Gene Encoding Gsalpha, XLalphas, and other Imprinted Transcripts.
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About 2.5 kb upstream of the Gsα promoter lies another promoter that drives the nearly ubiquitous expression of another transcript termed A/B (also termed 1A and 1’) [84-86]. The A/B promoter, despite being in close proximity to the Gsα promoter, reside within a DMR, where the maternal allele is methylated and repressed, while the paternal allele is non-methylated and active (Fig. 2). The first exon of the A/B transcript, as in NESP55 and XLαs, splices onto Gsα exons 2-13. However, exon A/B does not contain an in-frame translation initiation codon, and as supported by evidence from in vitro translation assays [86], translation can be initiated by an in-frame AUG located in exon 2, leading, presumably, to a variant of Gsα that has a truncated N-terminus. Transfection of COS cells with A/B cDNA results in the expression of a protein that localizes to the plasma membrane [86]. Based on these features, it is conceivable that the A/B protein interacts with adenylyl cyclase and may, therefore, exert a dominant negative effect on Gsα actions. This possibility remains to be investigated.