New Sensor For Cell Metabolites | March 12, 2012 Issue - Vol. 90 Issue 11 | Chemical & Engineering News
Volume 90 Issue 11 | p. 13 | News of The Week
Issue Date: March 12, 2012

New Sensor For Cell Metabolites

Chemical Biology: RNA-based detector monitors molecules in live cells
Department: Science & Technology
News Channels: Biological SCENE, Analytical SCENE
Keywords: sensor, RNA
Credit: Science
False-color image of an RNA-based sensor for detecting small molecule metabolites in cells.
Credit: Science
Credit: Science
A cartoon depicting the function of an RNA-based fluorescence sensor.
Credit: Science

Escherichia coli cells emit little fluorescence when analytes are not bound to the RNA sensors they contain (left) but turn green when analytes bind (right).

Tagging nonfluorescent molecules in live biological cells with fluorescent proteins has allowed researchers to visualize the hustle and bustle taking place in these membrane-bound metropolises and was an innovation that garnered the 2008 Nobel Prize in Chemistry.

Now, researchers led by Samie R. Jaffrey at Weill Cornell Medical College in New York City have developed a new sensor, based on RNA instead of protein, that can also use fluorescence to image small molecules and proteins in living cells (­Science, DOI: 10.1126/science.1218298). The new RNA sensors can likely be modified to detect a broad range of metabolites, including some that cannot currently be visualized with protein-based fluorescent tags.

This “alternative approach to image and study small-molecule metabolites is an important piece of work and will potentially have broad applications,” comments Taekjip Ha, who develops fluorescence-based imaging methods at the University of Illinois, Urbana-Champaign.

The sensor could find application in a wide range of research, from screening metabolites in cells involved in diabetes, neurodegenerative disease, or cancer to helping drug developers evaluate how their medicines are metabolized, Jaffrey says.

The new sensor relies on an RNA-fluorophore complex that Jaffrey and his colleagues reported last summer in Science (DOI: 10.1126/science.1207339). When an engineered RNA called Spinach interacts with the fluorophore 3,5-difluoro-4-hydroxybenzylidene imidazolinone(DFHBI), the complex produces a bright green color.

To make a sensor that can report the presence of specific biological molecules, Jaffrey’s team extended Spinach by adding a second RNA component that can bind different biological molecules or metabolites of interest, such as adenosine diphosphate, guanine, or S-adenosylmethionine.

When the molecule of interest is not bound, the sensor is unfolded and therefore cannot form a fluorescing complex. When the analyte is bound, the sensor is folded, binds DFHBI, and shines green.

Geoffrey F. Strouse, a chemist at Florida State University, notes that this new sensor faces a stumbling block inherent to many fluorescence-imaging methods—that inserting the RNA into cells may alter the production of metabolites one wishes to measure, a biological version of the Heisenberg uncertainty principle that observing a system inherently changes it. Nevertheless, he says the new approach is “a truly transformative development in molecular beacon technology.”

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mukesh lavkush bhaisare (March 14, 2012 2:20 PM)
thanks for sharing this RNA binding instead of protein but may be it is very costly and it needs high sensitive instruments to clarify this fluorescent.
What are the applied applications of this work.
thanks again for new rays of hope in research.

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