In the six months since this laboratory was established, we have made important progress in understanding the molecular basis of action of the glmS ribozyme-riboswitch. This is a gene-regulatory catalytic RNA that controls the synthesis of an essential precursor for the cell wall of Gram-positive bacteria. We had previously established that this RNA recruits a small molecule metabolite to carry out catalytic degradation of a mRNA. Our new studies demonstrate that the RNA active site not only binds to this small molecule, but actively perturbs its chemical properties to enhance catalysis. This is the first demonstration that RNA active sites are capable of such sophistication. This work is part of our effort to target the glmS ribozyme-riboswitch with artificial compounds that may provide leads for the development of new antibiotics. In addition, this RNA may also serve as a starting point for the development of new technologies that enable small-molecule directed RNA cleavage in vivo. Work in the development of new enabling technologies also included the structural characterization of a spectroscopic probe that allows accurate characterization of nucleic acid structure and dynamics employing EPR and fluorescence spectroscopies.

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National Heart, Lung, and Blood Institute
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Chen, Michael C; Tippana, Ramreddy; Demeshkina, Natalia A et al. (2018) Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36. Nature 558:465-469
Lau, Matthew W L; Trachman 3rd, Robert J; Ferré-D'Amaré, Adrian R (2017) A divalent cation-dependent variant of the glmS ribozyme with stringent Ca(2+) selectivity co-opts a preexisting nonspecific metal ion-binding site. RNA 23:355-364
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Zhang, Jinwei; Ferré-DAmaré, Adrian R (2016) Trying on tRNA for Size: RNase P and the T-box Riboswitch as Molecular Rulers. Biomolecules 6:
Zhang, Jinwei; Ferré-D'Amaré, Adrian R (2016) The tRNA Elbow in Structure, Recognition and Evolution. Life (Basel) 6:
Lau, Matthew W L; Ferré-D'Amaré, Adrian R (2016) In vitro evolution of coenzyme-independent variants from the glmS ribozyme structural scaffold. Methods 106:76-81
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Miao, Zhichao; Adamiak, Ryszard W; Blanchet, Marc-Frédérick et al. (2015) RNA-Puzzles Round II: assessment of RNA structure prediction programs applied to three large RNA structures. RNA 21:1066-84
Zhang, Jinwei; Ferré-D'Amaré, Adrian R (2015) Structure and mechanism of the T-box riboswitches. Wiley Interdiscip Rev RNA 6:419-33
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