A DNA switch for RNA folding

US researchers have equipped a large RNA domain with a DNA switch, which they say can fold or unfold the RNA molecule at will.¹ 

Chandrasekhar Miduturu and Scott Silverman at the University of Illinois at Urbana Champaign previously investigated the folding of a catalytic RNA molecule called a ribozyme.² This 51 kDa RNA molecule can easily be unfolded (or refolded) by removing (or adding) magnesium ions. 

The researchers cross-linked short DNA sequences (10-20 nucleotides) to specific positions in the RNA. They put two complementary DNA strands (which can form a double helix together) in suitable places, and were able to use the DNA double helix as a constraint which stops the RNA from adopting its normal folded structure.

Now they report that this constraint can be imposed and lifted reversibly in a variety of ways, such as offering competing single strand DNA molecules, or by using aptamer recognition, in which one of the DNA strands is designed to prefer binding to an organic molecule rather than assuming the double helix conformation.

The findings are welcomed by Jennifer Doudna from the University of California at Berkeley, US. ’This work demonstrates the feasibility of using cleverly engineered DNA molecules to control the folding of macromolecules, in this case a large RNA,’ said Doudna. 

But the technique is not limited to the world of nucleic acids, said Emanuele Paci from the University of Leeds, UK. ’Grabbing a molecule in two places and pulling its folded structure apart is something that people have done with proteins by AFM [atomic force microscopy]   for almost a decade,’ Paci told Chemistry World. ’This new technology is interesting, and maybe it can be transferred to protein folding or even to pathological misfolding.’

Michael Gross