Regulation of BRCA1 messenger RNA stability in human epithelial cell lines and during cell cycle progression

• Published in: FEBS letters 2007-07, Vol.581 (18), p.3435-3442
• Main Authors: Saunus, Jodi M., Edwards, Stacey L., French, Juliet D., Smart, Chanel E., Brown, Melissa A.
• Format: Article
• Language: English
• Subjects: 3′untranslated region; 3′UTR; Base Sequence; BRCA1; BRCA1 Protein - genetics; BRCA1 Protein - metabolism; Breast Cancer 1; Cell Cycle; Cell Line; Epithelial Cells - cytology; Epithelial Cells - metabolism; FACS; fluorescence-activated cell sorting; Gene Expression Regulation; Heterogeneous nuclear RNA; hnRNA; HO342; hoechst 33342; Humans; messenger RNA; Messenger RNA stability; mRNA; Post-transcriptional; Protein Processing, Post-Translational; REMSA; RNA Stability - genetics; RNA, Messenger - genetics; RNA-binding protein; RNA-BP; RNA-electrophoretic mobility shift assay; RNA–protein complex; RPC; Transcription, Genetic - genetics; ultraviolet cross-linking; UVX
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2007.06.046

The mechanisms regulating expression of breast cancer 1 (BRCA1) are not fully characterised. By studying regulation of endogenous BRCA1 in human epithelial cell lines and during cell cycle progression, we provide evidence to suggest BRCA1 is regulated post-transcriptionally at the level of messenger RNA stability. We also show that RNA-binding proteins associate with an AU-rich, cis-active sequence of the BRCA1 3′untranslated region in a cell cycle-dependent manner. Our data identify a new post-transcriptional regulatory axis and a novel mechanism for modulating the levels of BRCA1 protein, with possible implications for understanding the mechanisms underlying BRCA1 repression in breast cancer.