Newswise — New Brunswick, N.J. (Jan. 29, 2020) – Nearly 30 years after scientists first showed that RNA molecules can act as biological catalysts, researchers at Rutgers have discovered how an important RNA enzyme works in unprecedented detail.
The research, led by scientists at Rutgers–New Brunswick and University of Chicago and supported by the Rutgers Office of Advanced Computing Research, was published in the journal Nature Chemistry.
“Results from our study can be used to guide future design of new RNA-based biotechnology and medical therapies,” said senior author and principal investigator Darrin M. York, Henry Rutgers University Professor in the Department of Chemistry and Chemical Biology in the School of Arts and Sciences at Rutgers University–New Brunswick. He also directs the Laboratory for Biomolecular Simulation Research.
RNA helps form new molecules by reading the genetic information stored in DNA, resulting in proteins that play critical roles in the body’s tissues, organs, structure and functions. Scientists showed decades ago that certain RNA molecules also have a remarkable ability to catalyze complex chemical reactions, much like protein enzymes that are known to carry out thousands of chemical reactions within cells.
That discovery supported a hypothesis, known as the RNA World hypothesis, that earlier forms of life relied solely on RNA to store genetic information and catalyze chemical reactions. The discovery also led to the field of RNA catalysis, which has profoundly influenced our understanding of RNA’s diverse role in biology and led to new RNA-based technologies and medical therapies.
In the new study, scientists combined wide-ranging computational techniques and experiments to determine how the Varkud satellite ribozyme, an important RNA enzyme, catalyzes chemical reactions. They found that a metal ion (an electrically charged atom) plays a key role in the enzyme’s “active site” where the chemical reaction takes place.
“Our study allowed for the first time new links to be made between the Varkud satellite ribozyme and other classes of ribozymes, suggesting possible evolutionary connections,” York said.
The study made key predictions about the critical metal ion that, until now, had not been detected experimentally. The computational predictions were made by Abir Ganguly, a Rutgers assistant research professor in the Laboratory for Biomolecular Simulation Research, and co-lead author. Ganguly’s discovery stimulated experimental tests that confirmed the existence of the metal ion. Further simulations by Ganguly, coordinated with experiments at University of Chicago, showed how this metal ion can help speed up the reaction by more than a million-fold. The simulations performed by Ganguly used state-of-the-art “quantum mechanical force field” models developed at Rutgers by Timothy J. Giese, an associate research professor in York’s lab, who contributed to the study along with researchers at the University of Chicago and the Foundation for Applied Molecular Evolution.
The study: https://www.nature.com/articles/s41557-019-0391-x
For an interview with Professor York, contact Todd Bates at [email protected].
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