DEAD-box proteins function as nano-sized pistons, pushing open RNA strands to enable the formation of new cellular structures that is essential to the basic functioning of cells—a discovery that researchers say could aid in treatment of cancer and viruses in humans.
Researchers at the University of Texas at Austin discovered the mechanism in both normal and disease states behind the unwinding and separation of RNA strands in Mss116p, a DEAD-box protein found in yeast. The mechanism is almost certainly universal to all domains of life since DEAD-box proteins are found in all forms of living organisms, the research team concluded.
In their findings published Sept. 2 in Nature, the UT researchers explored a hypothesis from Anna Mallam, a postdoctoral researcher in the lab of study co-author Alan Lambowitz, Ph.D., the Nancy Lee and Perry R. Bass Regents Chair in Molecular Biology in the College of Natural Sciences, and director of the Institute for Cellular and Molecular Biology.
Mallam hypothesized that DEAD-box proteins function modularly, with one area on the protein (domain or “D”1) binding to an ATP molecule, the cell’s energy source, while another area (D2) binding to the double-stranded RNA.
“Once the second domain is latched on to the RNA and the first has got its ATP, the ‘piston’ comes down. It has a sharp edge that drives between the two strands and also grabs on one strand and bends it out of the way,” Mallam said in a statement.
The flexibility of DEAD-box proteins is hijacked in cancer, where their overexpression is believed to drive uncontrolled cell proliferation, as well as in infections caused by bacteria, fungi, and viruses, which rely on specific DEAD-box proteins for their propagation.
DEAD-box proteins are the largest family of RNA helicases, and crucial to RNA metabolism.
“This model explains key features of DEAD-box protein function and affords a new perspective on how the evolutionarily related cores of other RNA and DNA helicases diverged to use different mechanisms,” the team stated in the study.