Identification and functional analysis of novel BRCA1 transcripts, including mouse Brca1-Iris and human pseudo-BRCA1.
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.
Pettigrew
Christopher A
CA
School of Molecular and Microbial Sciences, University of Queensland, St. Lucia, QLD, Australia.
French
Juliet D
JD
Saunus
Jodi M
JM
Edwards
Stacey L
SL
Sauer
Aisha V
AV
Smart
Chanel E
CE
Lundström
Therese
T
Wiesner
Christiane
C
Spurdle
Amanda B
AB
Rothnagel
Joseph A
JA
Brown
Melissa A
MA
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*
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D012333:RNA, Messenger