A Sink for Signals
Triplex RNA motif binds cellular cGMP after expression in mammalian cells
The transmission of signals within cells is dependent on cyclic guanosine monophosphate (cGMP) as an important second messenger. Researchers led by Clemens Richert (Institut für Organische Chemie, University of Stuttgart) and Robert Feil (Interfakultäres Institut für Biochemie, University of Tübingen) developed a RNA motif that acts as a genetically encoded sink for cGMP molecules. As the motif can be repeated multiple times in a long continuous sequence, it was named “endless”.
cGMP is generated in many organ systems of mammals. It plays an important role in blood vessel relaxation and the regulation of blood pressure, and aberrant cGMP signaling might be related to cardiovascular disorders. Experimental manipulation of endogenous cGMP levels should lead to a better understanding of cGMP’s multiple functions in health and disease. While it is relatively simple to elevate intracellular cGMP levels in experiments, for example, by using nitric oxide (NO), it was not yet possible to lower intracellular cGMP concentrations artificially.
The newly developed cGMP-binding RNA motif “endless” is based on a triple helix. One of the three RNA segments forms a loop enclosing a binding cavity for cGMP (see Figure). The functionality of “endless” was tested in smooth muscle cells obtained from blood vessels. Live cell imaging with a cGMP biosensor was used to estimate levels of free cGMP in the cytosol. In cells that expressed an artificial “endless” gene, NO-induced cGMP signals were significantly suppressed in comparison to control cells. Thus, “endless” RNA acts as a sink for cGMP and should be very useful for future research on the physiological role of cGMP.
This work was supported by grants from the Deutsche Forschungsgemeinschaft.
Prof. Dr. Robert Feil
Interfakultäres Institut für Biochemie (IFIB)
72076 Tübingen, Germany
C. Kröner, M. Thunemann, S. Vollmer, M. Kinzer, R. Feil and C. Richert (2014). "Endless: A Purine-Binding RNA Motif that Can Be Expressed in Cells." Angewandte Chemie International Edition. Article first published online: 9 JUL 2014. DOI: 10.1002/anie.201403579
Link to Article: http://onlinelibrary.wiley.com/doi/10.1002/anie.201403579/abstractZurück