title: Bidirectional transcription from human LRRTM2/CTNNA1 and LRRTM1/CTNNA2 gene loci leads to expression of N-terminally truncated CTNNA1 and CTNNA2 isoforms.
abstract: 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.
authors.affiliation: Tallinn University of Technology, Department of Gene Technology, Akadeemia tee 15, Tallinn 12618, Harjumaa, Estonia.
authors.forename: Martin
authors.initials: M
authors.lastname: Kask
authors.forename: Priit
authors.initials: P
authors.lastname: Pruunsild
authors.forename: Tõnis
authors.initials: T
authors.lastname: Timmusk
mesh_terms: D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics; D017384:Sequence Deletion; D014158:Transcription, Genetic; D051178:alpha Catenin / Q000235:genetics*
chemical_list: C495273:CTNNA1 protein, human; C079671:CTNNA2 protein, human; C526971:LRRTM1 protein, human; C561320:LRRTM2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D051178:alpha Catenin