The 5′-flanking region of the rat GABAA receptor α2-subunit gene (Gabra2)

Abstract

The GABAA receptor α2-subunit gene (Gabra2) has a specific spatial and temporal pattern of expression in rat brain. As a first step towards understanding the molecular mechanism underlying this regulation, we have investigated the structural properties of the 5′-flanking region of the rat Gabra2 gene. We identified six α2 transcript isoforms, each of which differs only in the 5′-untranslated region (UTR). Alignment of cDNA and genomic DNA sequences revealed that six 5′-UTRs are generated from three alternative first exons by alternative splicing using internal and terminal 5′-splice donor sites present in these exons. Promoter regions containing multiple transcription initiation sites were identified in the 5′ proximity of each first exon. Two of these promoters lack TATA and CCAAT sequences. Finally, we have shown that differential activation of alternative promoters is used for the expression of the α2 mRNA isoforms during brain development, and that the diversity at the 5′-end of these transcripts affects GABAA receptor expression. Taken together, these results suggest that the expression of the Gabra2 gene can be influenced at both the transcriptional and post-transcriptional levels.