Just as people use metal detectors to scour the backyard for lost jewelry, Texas A&M University scientists, using their probing devices, explore structural information about metals in RNA molecules, believing the study may help invent medical drugs to cure hereditary diseases.

Chemical reactions within living cells require enzymes (biological catalysts) to proceed. Enzymes were thought to be proteins until the 1980s when scientists found that some enzymes are composed of catalytic RNA, which is not protein and requires metal ions to accelerate biochemical reactions.

Victoria J. DeRose, a chemistry professor at Texas A&M, is trying to understand how catalytic RNA tunes metal ions to perform chemical reactions.

"Genetic information flows from DNA via RNA to proteins, which in turn control different cells. So RNA's structure and function are very important," DeRose said. "We know a lot about how proteins get involved in chemical reactions, but how RNA can be a catalyst is poorly understood."

Most catalytic RNAs need metal ions to catalyze reactions, she said, and this is where bioinorganic chemistry comes into play.

"Catalytic RNA can block the synthesis of proteins," she said, "so, they can be very important as a drug."

DeRose's interdisciplinary research requires knowledge in biological chemistry, inorganic chemistry and physical chemistry. She collaborates with numerous other scientists in those fields.

To use catalytic RNA as a drug, it is necessary to be able to package it up and deliver it into a cell. For example, DeRose works with Texas A&M chemical engineers Mike Pishko and Aydin Akgerman to encapsulate RNA molecules in biodegradable polymers.

"We could implant a capsule near the cell, " she said, "and have the capsule release the RNA molecule as a drug."

Metal ions in catalytic RNA can provide a little window into their environment. Scientists can examine metal ions by using physics-orientated techniques, such as Electron Paramagnetic Resonance (EPR) and Nuclear Magnetic Resonance (NMR). One of DeRose's techniques, which combines EPR and NMR, simultaneously, probes metal ions in RNA molecules.

"The technique gives structural information about the metal ions," DeRose said. "That is important because we can not engineer RNA molecules to do different things until we know such information."

Catalytic RNA has potential applications in biotechnology and medicine. For example, genetically engineered plants can become virus resistant by producing a catalytic RNA to destroy the virus' gene.

DeRose and her collaborators are working on Hammerhead catalytic RNA, discoveries about which, she said, can be used in gene therapy.

"We have been studying how metal ions in Hammerhead [catalytic RNA] make catalysis work, and we found signals from one particular important metal site," DeRose said. "We now have great detail on how Hammerhead [catalytic RNA] carefully tunes this metal site to optimize catalysis activity."

She found this metal site is at a distance from the active site where catalysis occurs in Hammerhead RNA, meaning that the metal ion affects activity in a novel 'through-RNA' manner.

"How biomolecules work is an ever-changing challenge, and requires all the tricks of the trade," DeRose said. "We have to be multidisciplinary in order to cover all the bases to understand it."

Contact: Victoria J. DeRose, (979) 862-1401, DeRose@Mail.Chem.Tamu.Edu
Ping Wang, (979) 862-2694, pw@univrel.tamu.edu.

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