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DNA constraints control
structure of attached macromolecules
E. Kloeppel, Physical Sciences Editor
photo to enlarge
by Kwame Ross
Scott Silverman, right, a professor, and Chandrasekhar
Miduturu, a graduate student, use DNA to control the
folding and resulting structure of RNA.
CHAMPAIGN, Ill. —
A new method for manipulating macromolecules has been developed by researchers
at the University of Illinois at Urbana-Champaign. The technique uses
double-stranded DNA to direct the behavior of other molecules.
“Nature uses DNA as a building block to construct genes for storing
information,” said Scott Silverman, a professor of chemistry at Illinois. “We are using DNA to build structural constraints
that control the movement and shape of an attached macromolecule, RNA.”
In previous DNA nanotechnology efforts, duplex DNA has been used as
a static lattice to construct geometrical objects in three dimensions.
Instead of manipulating DNA alone into such shapes, the researchers
are using DNA to control the folding and resulting structure of RNA.
Eventually, they envision building supramolecular machines whose inner
workings are governed by twisted strands of DNA.
In a paper that has been accepted for publication in the Journal of
the American Chemical Society, and posted on its Web site, Silverman
and graduate student Chandrasekhar Miduturu begin with a piece of unfolded
RNA. Through specific chemical reactions, they attach two strands of
DNA, each resembling one side of a ladder. The two DNA strands spontaneously
bind together, then the researchers add magnesium ions to initiate folding
of the RNA.
“Folding of the RNA structure competes with formation of the DNA
constraint until a chemical balance is reached,” Silverman said.
“In some cases, the DNA is like a barnacle, just stuck onto the
RNA without perturbing its structure. In other cases, the DNA changes
the RNA structure. We can predict which situation will occur based on
the shape of the RNA and on the attachment points of the DNA constraint.”
In cases where the normal RNA shape and the DNA constraint cannot co-exist
simultaneously, the balance between competing RNA and DNA structures
is controlled by the concentration of magnesium ions, Silverman said.
In work not yet published, the researchers have also shown that the
effects of the DNA constraint on the RNA structure can be modulated
by external stimuli such as DNA oligonucleotide strands, protein enzymes
and chemical reagents.
While Silverman and Miduturu are currently using RNA as a proof of principle
for their DNA constraint studies, they also plan to use the new technique
to more effectively study the folding process of RNA. Because they can
control RNA structure precisely, they could generate and examine biologically
relevant folded and misfolded RNAs. They could also hook the DNA constraints
to other molecules, including non-biological macromolecules, to control
Importantly, the process of manipulating macromolecules with DNA constraints
can be either reversible or irreversible, depending on which chemical
trigger is used. Like a switch, a particular molecular shape could be
turned on and off.
“Another key aspect of DNA constraints is their programmability,”
Silverman said. “By placing two or more constraints on one molecule,
we could generate multiple molecular states that would be programmable
by DNA sequence. In other efforts, we would like to control macroscopic
assembly processes by influencing the shapes of self-assembling molecular
The David and Lucile Packard Foundation and the University of Illinois
funded the work.
note: To reach Scott Silverman, call 217-244-4489; e-mail: firstname.lastname@example.org.