Findings Redefine Mechanism Of Action Of RNA Helicase Enzymes

In order to carry out its functions, strands of RNA molecules will bind with other RNA molecules, making double-stranded RNA, or will bind with proteins, making RNA-protein complexes, or RNPs.

Wherever RNA occurs in the cell, ubiquitous RNA helicase enzymes are responsible for rearrangements of such complexes. RNA helicases are proteins that burn the universal cellular fuel molecule ATP and use the energy gained from this reaction to unwind double-stranded RNA. It has long been assumed that these enzymes, essential for all aspects of RNA metabolism, exclusively unwind double-stranded RNA.

In a new paper published in the April 30 issue of the journal Science, a group of researchers from the Case Western Reserve University School of Medicine provide fundamental new insight into the function of RNA helicases (also called DExH/D-RNA helicases). The paper is titled "Protein Displacement by DExH/D 'RNA Helicases' Without Duplex Unwinding."

"We provide direct evidence that these enzymes can utilize energy gained from burning ATP to change shape and composition of RNA-protein complexes without unwinding RNA duplexes," said senior author Eckhard Jankowsky, Ph.D., assistant professor of biochemistry at Case.

"We show that two different RNA helicases can displace proteins from single-stranded RNA and that duplexes do not necessarily need to be disrupted by the enzymes during their myriad biological functions. The findings essentially redefine the mechanism of action of RNA helicases and constitute a paradigm shift in assessing roles of these enzymes in virtually all biological processes that involve RNA."

In an accompanying perspective article, Patrick Linder of the Department of Microbiology and Molecular Medicine, University of Geneva, Switzerland, writes, "Their findings provide new insights into the dynamic rearrangements that take place in RNPs [RNA-protein complexes], and the mechanism of RNA duplex unwinding by RNA helicases."

The work was conducted in the Department of Biochemistry and the Center for RNA Molecular Biology by Jankowsky's group in collaboration with a laboratory group of Timothy Nilsen, Ph.D., director of the RNA Center at Case. The other authors are, from the Department of Biochemistry, Margaret E. Fairman, Wen Wang, and Heath A. Bowers, and, from the RNA Center, Patricia A. Maroney, as well as, from the Department of Biological Sciences, State University of New York at Buffalo, Paul Gollnick.