α-Catenins (CTNNAs) are essential for the regulation of cell-cell and cell-matrix interactions in tissues. All human CTNNA genes contain antisense oriented leucine rich repeat transmembrane (LRRTM) genes within their seventh introns. Recently, a haplotype upstream of one of the human LRRTM genes, LRRTM1 that resides in CTNNA2, was shown to be associated with handedness and schizophrenia. Here, we show that both CTNNA1 and CTNNA2 contain alternative 5' exons linked to bidirectional promoters that are shared with the antisense oriented LRRTM2 and LRRTM1 genes, respectively. We demonstrate that bidirectional activity of these promoters results in alternative CTNNA1 and CTNNA2 transcripts that are expressed at high levels in the nervous system and show that N-terminally truncated CTNNA1 and CTNNA2 proteins lacking the β-catenin interaction domain are produced from these alternative CTNNA mRNAs. In addition, our results indicate that the haplotype that affects LRRTM1 expression and is associated with schizophrenia and handedness, could also influence the expression of brain-enriched alternative transcripts of CTNNA2.
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