NAR breakthrough discovery: RNA's 'on' and 'off'

Similar to light switches, RNA switches (called riboswitches) determine which genes are turned "on" and "off

Now, researchers led by Northwestern University and the University at Albany have discovered that one part of RNA is able to smoothly invade and displace another part of the same RNA, allowing its structure to rapidly and dramatically change shape

Using a simulation they started last year, the researchers made this discovery by looking closely at a slow-motion simulation of the ribosomal switch

This finding may have potential implications for the design of new RNA-based diagnostics, as well as for the design of successful drugs targeting RNA to treat diseases

The research is described in a new paper published today (March 28) in the journal Nucleic Acids Research (NAR), which it dubs a "breakthrough article" that answers long-standing questions

"We have found this strand displacement mechanism in other types of RNA molecules, suggesting that this may be a potential universality of RNA folding," said Northwestern's Julius B.

Lukes is a professor of chemical and biological engineering in Northwestern's McCormick School of Engineering and a member of the Center for Synthetic Biology and the Institute for Life Process Chemistry

Groundbreaking approach to R2D2

Although RNA folds more than 10 quadrillion times per second in the human body—every time a gene is expressed in a cell—researchers know very little about this process

R2D2 utilizes a technology platform developed in the Lux lab to capture data related to RNA folding during RNA synthesis

Dr.

long distance communication

Lucks and Chen's previous simulations showed the folding of an ancient RNA called SRP, while the new movie simulates a riboswitch in Bacillus subtilis, a bacterium commonly found in soil

Riboswitches have two basic parts

"It's odd that they're so far apart, but the molecules that bind can cause large functional changes," Lacks said

Fortunately, Chen and their team discovered that riboswitches may transmit information downstream through a chain-displacement mechanism
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In response to chemical binding, the chain-exchange process triggers a structural switch between "on" and "off" states
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Optimizing RNA for Drugs and Diagnostics

Armed with this new insight, Lucks believes the stage has come to optimize riboswitches to perform useful tasks
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Such switches could be used in synthetic biology-based diagnostics, for example, to be "turned on" in the presence of environmental pollutants
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Researchers will also learn lessons from studying this riboswitch to find new ways to make RNA-targeting drugs or new antibiotics
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"Many diseases are likely caused by something going wrong at the RNA level," Lacks said
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"The more we know about this, the better we can design RNA-targeted drugs and RNA therapeutics
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article title

Cotranscriptional RNA strand exchange underlies the gene regulation mechanism in a purine-sensing transcriptional riboswitch