In the past two decades, methods have been developed to pull on and twist individual DNA molecules, and the response of double-stranded DNA to applied forces and torques (i.e. molecules under twist) has been mapped out with increasing precision. In contrast, much less is known about the mechanical response of RNA, DNA’s molecular cousin. Chemically, RNA is very similar to DNA and like DNA, it can form a double-stranded helix. Yet in the cell, RNA carries our very different functions: RNA is a central player in translating the genetic information (stored in DNA) into proteins, which in turn carry out most metabolic functions in the cell. In addition, there are several more recently discovered mechanisms how RNA is involved in regulating the expression of genes, i.e. controlling the way the genetic code is executed.

A team of researchers led by Jan Lipfert (now at the LMU Munich) and Nynke H. Dekker have used magnetic tweezers to determine how double-stranded RNA responds to external forces and torques. In their magnetic tweezers instruments, single double-stranded RNA molecules are tethered. Using magnets, the researchers can apply precisely controlled forces and twists to the RNA molecules.
They found that if the forces and torques are not too large, double-stranded RNA bends and twists elastically, like a rubber rod. However, when the forces and torques become too large, the molecular structure rearranges and RNA undergoes - sometimes dramatic - structural changes. From the measurements, the elastic constants of double-stranded RNA were determined. The elastic properties for bending, twisting, and stretching were found to be quite similar to DNA.

When the researchers measured another elastic constant, the so-called twist-stretch coupling, they made a surprising discovery: While DNA lengthens when the helix is overwound, RNA shortens. Another surprise came when the researchers used again magnetic tweezers to measure the dynamics of forming a loop, where RNA exhibited 100-times slower dynamics than DNA.
Current models of DNA and RNA fail to explain these surprising findings and the current work poses an open challenge to molecular modeling approaches.
The results present for the first time a complete picture of how double-stranded RNA responds to forces and torques. They serve as a baseline to model and understand RNA in more complex biological or technological contexts and reveal unexpected properties of this key building block in molecular biology.

“Double-stranded RNA under force and torque: Similarities to and striking differences from double-stranded DNA”
Jan Lipfert, Gary M. Skinner, Johannes M. Keegstra, Toivo Hensgens, Tessa Jager, David Dulin, Mariana Köber, Zhongbo Yu, Serge P. Donkers, Fang-Chieh Chou, Rhiju Das, and Nynke H. Dekker
PNAS, published online October 13, 2014

Contact
Prof. Jan Lipfert
Department of Physics
LMU München
Amalienstr. 54
80799 München
Duitsland
jan.lipfert@lmu.de
+49-89-2180 2005

Prof. Nynke H. Dekker
Afdeling Bionanoscience
TU Delft
Lorentzweg 1
2628 CJ Delft
Nederland
n.h.dekker@tudelft.nl
015-2783219