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The left panel illustrates the structure of a metal-binding RNA. Each nucleotide is colored according to its experimentally-determined exposure to the outside solvent. Blue nucleotides tend to be buried inside the structure, and red nucleotides are mostly
In a paper published April 16, 2012 in the journal Nature Methods, a team from the University of North Carolina at Chapel Hill demonstrates a simple, cost-effective technique for three-dimensional RNA structure prediction that will help scientists understand the structures, and ultimately the functions, of the RNA molecules that dictate almost every aspect of human cell behavior. When cell behavior goes wrong, diseases – including cancer and metabolic disorders – can be the result.
Over the past five decades, scientists have described more than 80,000 protein structures, most of which are now publicly available and provide important information to medical researchers searching for targets for drug therapy. However, a similar effort to catalogue RNA structures has mapped only a few hundred RNA molecules. As a result, the potential of RNA molecules has just barely been developed as targets for new therapeutics.
“To effectively target these molecules, researchers often need a three-dimensional picture of what they look like,” says Nikolay Dokholyan, PhD, professor in the department of biochemistry and biophysics, and the project’s co-leader.
“With Dr. Kevin Weeks’ lab, we have developed a way to create a three-dimensional map of complex RNAs that are not amenable to study through other methods. It builds on information from a routine laboratory experiment, used in the past to evaluate RNA models from a qualitative standpoint. Our team has created a sophisticated quantitative model that uses this simple information to predict structures for large, complex RNA molecules, which have previously been beyond the reach of modeling techniques,” he adds.
Dokholyan is a member of UNC Lineberger Comprehensive Cancer Center and director of the UNC Center for Computational and Systems Biology, hopes that the method will help researchers who are trying to target RNAs molecules to change cellular metabolism in a way that ultimately reduces the effects of cellular diseases like cancer. He notes, “Rational, cost-effective screening for small molecules requires a good understanding of the targeted structure. We hope that this method will open doors to new findings applicable to a wide range of human diseases.”
Other members of the research team include Feng Ding, PhD, Research Assistant Professor of biochemistry and biophysics, Christopher Lavendar, a graduate student of in the department chemistry, and study co-leader Kevin Weeks, PhD, Kenan Distinguished Professor of Chemistry, College of Arts and Sciences, and UNC Lineberger member.
- Faculty News
ASBMB Today highlights Henrik Dohlman as a new JBC associate editor
Learn more about Henrik Dohlman, professor and vice chair of biochemistry and biophysics, from his profile highlight in ASBMB Today's December 2013 issue.
Sharon Campbell organizes the ASBMB Special Symposia Series to be held July 2014
Learn more about the event "Translating the Biophysics of Molecular Switches: Signaling Mechanisms and Inhibition of Ras and Rho GTPases"
New findings from the Carter lab challenge assumptions about origins of life
Dr. Charles Carter, Jr., Professor of Biochemistry and Biophysics resurrect “molecular fossils” to conduct experiments that undercut the predominant scientific theory of how life began on Earth.
Congratulations to Greg Wang, Assistant Professor of Biochemistry and Biophysics, who was awarded a Jefferson Pilot Fellowship from UNC School of Medicine to further his research mission searching for better ways to shut down cancer cells.
- Postdoc & Scholars News
2013 Retreat Winners
Scott Rothbart receives a 2013 UNC Pagano Award for a best first-author postdoctoral paper
Congratulations to Dr. Scott Rothbart, a postdoctoral fellow in Dr. Brian Strahl's lab who is one of the recipients this year of a Joseph S. Pagano award
Shobhan Gaddameedhi receives CEHS-2013 Pilot Project Award
Congratulations to Dr. Shobhan Gaddameedhi, postdoctoral fellow in Dr. Aziz Sancar's lab, received $25,000 from the Center for Environmental Health and Susceptibility 2013 Pilot Project Award.
Rothbart receives a 2013 Postdoctoral Award for Research Excellence
Congratulations to Dr. Rothbart, postdoctoral fellow in the lab of Dr. Brian Strahl, Associate Professor of Biochemistry and Biophysics, who received a 2013 Postdoctoral Award for Excellence in Research at UNC.