It is of interest to note the functional importance of exons 10 and 17, which showed decreased expression in alcoholic brains. Exon 10 is known to participate in GABA binding to the receptor (7, 39). A loss of GABA binding sites would likely diminish GABA response, and signal transduction resulting from receptor activation would be less efficient. Exon 17 contains the entire TM 3 as well as intracellular and extracellular regions between neighboring TMs. G proteins bind to the intracellular region between TM 3 and 4 (7), and without exon 17 GABAB receptors are not able to transfer signals through G proteins. At exon 23, alcoholic brains showed a RPJM decrease of a novel splice junction that is a potential target for miRNAs at 3’ UTR. Therefore, decrease of the miRNA target site splicing-out would result in more of this target site in alcoholic brains. This could allow miRNAs to destabilize GABAB1 transcripts that contain the miRNA target site including the major GABAB1 splicing variant as well as some short splicing variants. Although overall GABAB1 gene expression does not change in alcoholic brains, an increase in abnormal variants could nevertheless decrease the fraction of normal GABAB receptors.
