Gene regulation is an essential element for success in all living organisms. Typically, regulatory molecules that turn genes on or off are composed of some biomolecules other than nucleic acids. Now, synthetic biologists at Cornell University have created molecular switches composed entirely of RNA. 

These engineered RNA molecules, called small transcription activating RNAs or STARs, were designed to disrupt the formation of an inherent transcription terminator within E. coli. Generation of the STARs is described in a study released yesterday by Nature Chemical Biology under the title “Creating Small Transcription Activating RNAs”.

“We've created a whole new toolset of regulation,” said Julius Lucks, Ph.D., assistant professor of chemical and biomolecular engineering and senior author of the study, who subsequently also describes RNA as “the most engineerable molecule on the planet.”

RNA, along with DNA and proteins, is one of the three major macromolecules essential for life and is a single-stranded close relative to DNA. While RNA has many functions within the cellular environment, such as coding and decoding, its role in gene expression regulation was of great interest to Dr. Luck and his team. One thing RNA cannot do is begin the regulatory process by tuning on or activating transcription, which is the first essential step in gene expression.   

“RNA is like a molecular puzzle, a crazy Rubik's cube that has to be unlocked in order to do different things,” stated Dr. Lucks. “We've figured out how to design another RNA that unlocks part of that puzzle. The STAR is the key to that lock.”

The Cornell team engineered an RNA system that acts like a genetic switch telling the cell to begin the transcription process for a specific gene.  Specifically, the STAR system requires a special RNA sequence being placed upstream of a genetic element that typically acts as a transcriptional block for the gene downstream. When STAR is in place, it prevents transcription of the downstream gene from being turned off by the normal regulatory elements.

Dr. Luck envisions engineered RNA gene networks that may offer diagnostic capabilities for the future. This is going to open up a whole set of possibilities for us, because RNA molecules make decisions and compute information really well, and they detect things really well,” concluded Dr. Lucks.

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