News

Crystal structure of the preQ1-II riboswitch.

Department of Biochemistry and Biophysics Associate Professor Joseph Wedekind and members of his research group (Joseph Liberman, Mohammad Salim and Jolanta Krucinska) published a paper in the June 2013 issue of Nature Chemical Biology. The work describes the structure of an RNA molecule called the preQ1 class II riboswitch (featured on the journal's cover) that functions as a gene regulatory element for bacteria within the Firmicutes phylum, including human pathogens such as Streptococcus pneumoniae. The RNA structure is bound to the small molecule preQ1, which is the last soluble metabolite in the biosynthetic pathway that produces queuosine, a hypermodified base at the wobble position of certain tRNAs that promotes accurate genetic decoding. Because preQ1 is unique to the bacterial metabolome, the class II preQ1 riboswitch has potential as an antibacterial drug target.

The research was performed primarily at the University of Rochester and made extensive use of the Structural Biology and Biophysics Facility. The work also required the Stanford Synchrotron Radiation Lightsource (Menlo Park, CA), as well as Cornell High Energy Synchrotron Source (Ithaca, NY) where crystals were subjected to X-ray diffraction analyses. The work in Wedekind' lab was funded by the National Institutes of Health/ National Institute for General Medical Sciences (NIH/NIGMS).

The preQ1-II riboswitch structure reveals the chemical details of preQ1 binding in a pocket formed at the junction of three RNA helices. Complementary work from Wedekind's lab showed that preQ1 promotes a more compact shape that leads to blocking of a signal that is necessary for protein synthesis, which leads to lower levels of preQ1 in the cell. Of special note was the lab's observation that the mechanism of action used by the preQ1-II RNA riboswitch is entirely different than that used by the class I preQ1 riboswitch, whose structure and mode of preQ1 binding were reported previously by Wedekind's lab. Overall the results expand the known repertoire of metabolite-binding modes used by regulatory RNAs.