Identification of the breast cancer susceptibility gene BRCA2

Identification of the breast cancer susceptibility gene BRCA2

22 FEBRUARY 1996 | Richard Wooster, Graham Bignell, Jonathan Lancaster, Sally Swift, Sheila Seal, Jonathan Mangion, Nadine Collins, Simon Gregory, Curtis Gumbs, Gos Michlem, Rita Barfoot, Rifat Hamoudi, Sandeep Patel, Catherine Rice, Patrick Biggs, Yasmin Hashim, Amanda Smith, Frances Connor, Adelgier Arason, Julius Gudmundsson, David Ficenec, David Kelsell, Deborah Ford, Patricia Tonin, D. Timothy Bishop, Nigel K. Spurr, Bruce A. J. Ponder, Rosalind Eeles, Julian Peto, Peter Devilee, Cees Cornelisse, Henry Lynch, Steven Narod, Gilbert Lenoir, Valdgardur Egilsson, Rosa Bjork Barkdottir, Douglas F. Easton, David R. Bentley, P. Andrew Futreal, Alan Ashworth & Michael R. Stratton
The homeodomain of the protein bicoid (bcd) is sufficient for binding to cad mRNA, while other homeodomain proteins, such as orthodenticle and antenapedia, do not bind. This in vitro interaction is consistent with in vivo observations, suggesting that the bcd homeodomain is necessary for the formation of the cad gradient. The failure of other homeodomain proteins to bind cad mRNA does not rule out the possibility that they possess RNA-binding properties, as some zinc-finger-type transcription factors do. To assess the functional significance of the bcd-cad mRNA interaction, co-transfection experiments were performed in Drosophila Schneider cells. Reporter gene constructs containing different 3' UTR sequences were used, and the translation efficiency of CAT mRNAs was measured. CAT mRNAs with the Drosophila cad 3' UTR or the BBR region produced less CAT activity than those with the Clognia cad 3' UTR or the 3' half of the Drosophila cad 3' UTR. These results suggest that bcd may act as a transcriptional activator and also reduce the translation efficiency of BBR-containing mRNAs. Further experiments showed that bcd suppresses the translation of BBR-containing mRNA. This is consistent with the idea that bcd acts as a transcriptional activator and functions similarly to key components of the posterior maternal pattern-organizer system, which acts through translational repression. The results imply that the asymmetric distribution of key components of the anterior and posterior maternal pattern-forming systems is linked through the dual function of bcd.The homeodomain of the protein bicoid (bcd) is sufficient for binding to cad mRNA, while other homeodomain proteins, such as orthodenticle and antenapedia, do not bind. This in vitro interaction is consistent with in vivo observations, suggesting that the bcd homeodomain is necessary for the formation of the cad gradient. The failure of other homeodomain proteins to bind cad mRNA does not rule out the possibility that they possess RNA-binding properties, as some zinc-finger-type transcription factors do. To assess the functional significance of the bcd-cad mRNA interaction, co-transfection experiments were performed in Drosophila Schneider cells. Reporter gene constructs containing different 3' UTR sequences were used, and the translation efficiency of CAT mRNAs was measured. CAT mRNAs with the Drosophila cad 3' UTR or the BBR region produced less CAT activity than those with the Clognia cad 3' UTR or the 3' half of the Drosophila cad 3' UTR. These results suggest that bcd may act as a transcriptional activator and also reduce the translation efficiency of BBR-containing mRNAs. Further experiments showed that bcd suppresses the translation of BBR-containing mRNA. This is consistent with the idea that bcd acts as a transcriptional activator and functions similarly to key components of the posterior maternal pattern-organizer system, which acts through translational repression. The results imply that the asymmetric distribution of key components of the anterior and posterior maternal pattern-forming systems is linked through the dual function of bcd.
Reach us at info@futurestudyspace.com