A new method of silencing gene expression is reported in the September issue of Nature Chemical Biology. By targeting DNA transcription start sites with peptide nucleic acids (PNAs) researchers have blocked a protein connected to the spread of certain tumours. When bound to the human progesterone receptor (hPR) start site, PNA blocks hPR production, resulting in the upregulation of ezrin, a protein associated with the metastasis of some tumours.
Transcription -- the conversion of genes into RNA copies -- is initiated at sites where polymerase enzymes bind to DNA. Corey and coworkers hypothesized that these transcriptional start sites may be ideal targets for gene silencing approaches. To demonstrate their approach, they targeted the transcription start site of the hPR DNA with an antigene PNA (agPNA). agPNAs directed toward one form of the receptor, hPR-B, potently inhibited hPR-B mRNA production, but also reduced the mRNA levels of hPR-A, a receptor variant. These results suggested an unknown regulatory link between hPR-B and hPR-A expression. Downregulation of hPR in tumor cells by agPNAs changed cell development and enhanced the expression of ezrin, a cytoskeletal protein known to be involved in the metastasis of certain tumors.
The authors showed the usefulness of their approach by blocking gene transcription in live diseased cells, allowing direct observation of the effects of gene silencing. Because every gene contains a DNA transcription start site, this method of controlling transcription initiation could offer a powerful tool for studying cellular processes and potentially treating diseases such as cancer.
David R. Corey
University of Texas Southwestern Medical Center, Dallas, TX, USA)
Additional contact for comment on paper:
Carnegie Mellon University, Pittsburgh, PA, USA)
Abstract available online.
(C) Nature Chemical Biology press release.
Message posted by: Trevor M. D'Souza