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-Δ22, 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.
Keywords BRCA1 - Brca1 - Splice variant - Pseudogene - Brca1-Iris
Christopher A. Pettigrew, Juliet D. French, and Jodi M. Saunus contributed equally to the work.