Artificial Gene Regulation by RNA Molecules
X-ray crystal structure of a novel complex between NF-kappaB protein (ribbons) and two folded RNA molecules (spheres).
It was once believed possible that all genes were regulated by the binding of RNA molecules to the DNA double helix. This model is not generally true, but it provides a foundation to explore whether artificial RNA molecules can be selected for the ability to control genes in cells. The Maher Lab is studying several approaches to this question.
The historical observation that transcription factor IIIA (TFIIIA) can bind both DNA and RNA made Dr. Maher's team curious if artificial tight-binding RNAs could be selected for other transcription factors. Expression of such RNA inhibitors in cells might down-regulate genes that respond to the target transcription factor.
The Maher Lab's initial studies involve small RNAs that the team selected for binding and inhibition of the NF-kappaB transcription factor. Inhibition of this protein could be of value against HIV-1 replication, inflammation and in enhancing tumor cell suicide after chemotherapy, all processes involving NF-kappaB. The lab's work involves biochemistry with purified molecules as well as the use of genetic screens and selections with microorganisms such as bacteria and yeast.
Ongoing studies seek to identify potential RNA aptamer inhibitors for hundreds of human transcription factors and to explore transcription factor inhibition in mammalian cells. Other research seeks to determine if RNA molecules can deliver gene regulatory proteins to new genes in cells.