Scott Silverman and Elena Zelin from the University of Illinois at Urbana-Champaign have made important advances in the regulation of ribozyme function. They found that double-stranded DNA constraints enable efficient control of catalysis by a large multi-domain group I intron ribozyme.

Large RNA molecules assume conformations in which they are catalytically active. The structure of RNA can be controlled by attachment of two single DNA strands at strategically chosen positions of the RNA molecule. The two DNA strands interact to form a double-helical constraint that forces the RNA molecule to adopt a misfolded conformation in which it is catalytically inactive. 

Controlling the catalysis of a small single-domain ribozyme, the hammerhead ribozyme, has been shown previously. Now Silverman has found that DNA constraints can efficiently control the catalysis of a much larger 388 nt multidomain Tetrahymena group I intron ribozyme. DNA constraints were used to force the group I intron RNA into a stable misfolded conformation where the ribozyme catalysis is almost completely suppressed. 

'Among other applications, we envision that this DNA constraint strategy to control catalysis of large RNA molecules will be useful for investigating fundamental aspects of RNA folding landscapes, by providing well-defined misfolded starting points for future folding experiments', says Silverman. 

Kathryn Sear