In the past year, we have made important progress in our understanding of the mechanism of action of two regulatory RNAs that respond to amino acid starvation in a variety of bacteria, including clinically important pathogens of genera such as Bacillus and Vibrio. The glycine riboswitch is thus far unique among gene-regulatory RNAs in that its architecture involves quaternary interactions. We have used solution methods to analyze how these interactions between independently folded, homologous subunits gives rise to function. The T-box riboswitch controls the expression of aminoacyl-tRNA synthetases, the enzymes responsible for specific charging of tRNA with amino acids, in response to intracellular amino acid levels in Gram-positive bacteria. It is essential for cell survival and virulence. Although this mRNA domain was discovered in 1993, it was not until our work published this year that the mechanism by which the T-box specifically recognizes tRNA was elucidated. In addition to resolving a long-standing question mechanistic, our work forms the starting point for analysis of RNA-RNA interactions in biological systems.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2013
Total Cost
$941,172
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Meyer, Peter A; Socias, Stephanie; Key, Jason et al. (2016) Data publication with the structural biology data grid supports live analysis. Nat Commun 7:10882
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
Zhang, Jinwei; Ferré-D'Amaré, Adrian R (2016) The tRNA Elbow in Structure, Recognition and Evolution. Life (Basel) 6:
Zhang, Jinwei; Ferré-DAmaré, Adrian R (2016) Trying on tRNA for Size: RNase P and the T-box Riboswitch as Molecular Rulers. Biomolecules 6:
Ferré-D'Amaré, Adrian R (2015) On the shoulders of giants. RNA 21:504-5
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) Post-crystallization Improvement of RNA Crystal Diffraction Quality. Methods Mol Biol 1316:13-24
Zhang, Jinwei; Ferré-D'Amaré, Adrian R (2015) Structure and mechanism of the T-box riboswitches. Wiley Interdiscip Rev RNA 6:419-33
Warner, Katherine Deigan; Chen, Michael C; Song, Wenjiao et al. (2014) Structural basis for activity of highly efficient RNA mimics of green fluorescent protein. Nat Struct Mol Biol 21:658-63
Zhang, Jinwei; Ferré-D'Amaré, Adrian R (2014) Dramatic improvement of crystals of large RNAs by cation replacement and dehydration. Structure 22:1363-71

Showing the most recent 10 out of 21 publications