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Three-state mechanism couples ligand and temperature sensing in riboswitches

15. Juli 2013. Riboswitches are gene-regulatory RNA elements that can function at the level of transcription, translation and RNA cleavage. The commonly accepted mechanism for riboswitch function proposes a ligand-dependent conformational switch between two mutually exclusive states. According to this model, ligand binding to an aptamer domain induces an allosteric conformational switch of an expression platform, leading to activation or repression of ligand-related gene expression.

Many riboswitch properties, however, cannot be explained by such a pure two-state mechanism. A research team led by Harald Schwalbe now demonstrated that the regulation mechanism of the adenine-sensing riboswitch, encoded by the add gene on chromosome II of the human Gram-negative pathogenic bacterium Vibrio vulnificus, is indeed different from a two-state switch mechanism as it involves three distinct stable conformations. The team characterized the temperature and Mg dependence of the population ratios of the three conformations and the kinetics of their interconversion at nucleotide resolution. The observed temperature dependence of a pre-equilibrium involving two structurally distinct ligand-free conformations of the add riboswitch conferred efficient regulation over a physiologically relevant temperature range. The scientists consider such robust switching a key requirement for gene regulation in bacteria that have to adapt to environments with varying temperatures. To our knowledge, the translational adenine-sensing riboswitch represents the first example of a temperature-compensated regulatory RNA element.

Figure showing the three different states of the riboswith. In the background an electron microscope image of the bacterium Vibrio vulnificus (magnification x13000; CDC Public Library Janice Haney Carr and James Gathany)


Contact: Harald Schwalbe, Institute of Organic Chemistry and Chemical Biology, Riedberg Campus, Goethe University Frankfurt, Tel.: +49 (0)69 798-29130, schwalbe@em.uni-frankfurt.de

Publication: Anke Reining, Senada Nozinovic, Kai Schlepckow, Florian Buhr, Boris F├╝rtig und Harald Schwalbe. 2013. Three-state mechanism couples ligand and temperature sensing in riboswitches, Nature, DOI: 10.1038/nature12378. Link to full paper