Identification and functional analysis of novel BRCA1 transcripts, including mouse Brca1-Iris and human pseudo-BRCA1

Christopher A. Pettigrew, Juliet D. French, Jodi M. Saunus, Stacey L. Edwards, Aisha V. Sauer, Chanel E. Smart, Therese Lundström, Christiane Wiesner, Amanda B. Spurdle, Joseph A. Rothnagel, Melissa A. Brown

Research output: Contribution to journalArticle

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-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.

Original languageEnglish
Pages (from-to)239-247
Number of pages9
JournalBreast Cancer Research and Treatment
Volume119
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • BRCA1
  • Brca1
  • Brca1-Iris
  • Pseudogene
  • Splice variant

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Pettigrew, C. A., French, J. D., Saunus, J. M., Edwards, S. L., Sauer, A. V., Smart, C. E., Lundström, T., Wiesner, C., Spurdle, A. B., Rothnagel, J. A., & Brown, M. A. (2010). Identification and functional analysis of novel BRCA1 transcripts, including mouse Brca1-Iris and human pseudo-BRCA1. Breast Cancer Research and Treatment, 119(1), 239-247. https://doi.org/10.1007/s10549-008-0256-2