Until now, however, it was not clear exactly how the synthetic RNA strands affected that mix of regulating proteins.
In the current study, also carried out in cancer cell cultures, the UT Southwestern research team discovered an unexpected target for the manufactured RNA. The RNA did not home in on the gene itself, but rather on another type of RNA produced by the cell, a so-called noncoding RNA transcript. This type of RNA is found in association with the promoter regions that occur in front of the gene. Promoter regions, when activated, act essentially as a "start" command for turning on genes.
The researchers found that their man-made RNA strand bound to the RNA transcript, which then recruited certain proteins to form an RNA-protein complex. The whole complex then bound to the promoter region, an action that could then either activate or inhibit gene expression.
"Involvement of RNA at a gene promoter is a new concept, potentially a big new concept," Dr. Janowski said. "Interactions at gene promoters are critical for understanding disease, and our results bring a new dimension to understanding how genes can be regulated."
Until recently, many scientists believed that proteins alone control gene expression at promoters, but Drs. Corey and Janowski's results suggest that this assumption is not necessarily true.
"By demonstrating how small RNAs can be used to recruit proteins to gene promoters, we have provided further evidence that this phenomenon should be in the mainstream of science," Dr. Corey said.
Although using synthetic RNA to regulate gene expression and possibly treat disease in humans is still in the future, Dr. Corey noted that the type of man-made RNA molecules employed by the UT Southwestern team are already being used in human clinical trials, so progress
|Contact: Amanda Siegfried|
UT Southwestern Medical Center