title: Identification and functional analysis of novel BRCA1 transcripts, including mouse Brca1-Iris and human pseudo-BRCA1.
abstract: Recent characterization of the mammalian transcriptome has confirmed its predicted complexity, with many loci encoding multiple splice variants and pseudogenes. The breast cancer susceptibility gene BRCA1 is a tumour suppressor gene that produces multiple functional transcripts. For example, BRCA1-IRIS is a splice variant of BRCA1, which encodes a protein that is functionally distinct from BRCA1. Here we describe the identification of ten novel Brca1 splice variants including Brca1-Iris, the mouse orthologue of human BRCA1-IRIS. We show that Brca1-Iris is differentially expressed during mammary epithelial differentiation and regulates survival of mammary epithelial cells. Another transcript, Brca1-Delta22, expressed in both mouse and human cells, was found to be defective in transcriptional activation capacity. Finally, we show that the human BRCA1 pseudogene produces a spliced pseudoBRCA1 transcript. The identification of these transcripts has implications for the understanding of the role of BRCA1 in biology and disease and for the interpretation of mouse knockout models.
authors.affiliation: School of Molecular and Microbial Sciences, University of Queensland, St. Lucia, QLD, Australia.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Pettigrew
authors.forename: Juliet D
authors.initials: JD
authors.lastname: French
authors.forename: Jodi M
authors.initials: JM
authors.lastname: Saunus
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Edwards
authors.forename: Aisha V
authors.initials: AV
authors.lastname: Sauer
authors.forename: Chanel E
authors.initials: CE
authors.lastname: Smart
authors.forename: Therese
authors.initials: T
authors.lastname: Lundström
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiesner
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Rothnagel
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D005821:Genetic Techniques; D006367:HeLa Cells; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D011544:Pseudogenes; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D012333:RNA, Messenger