Abstract

In the past year, we have made important progress in our understanding of the mechanism of action of a class of regulatory RNAs that respond to amino acid starvation in a variety of bacteria, including clinically important pathogens of genera such as Bacillus and Listeria. The T-box riboswitches control 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 lst year that the mechanism by which the T-box specifically recognizes tRNA was elucidated. This year, we have uncovered the mechanism employed by the RNA to evaluate the aminoacylation (charge) state of tRNA, allowing it to respond to starvation. We have also explored the molecular underpinnings for the ability of the glmS ribozyme-riboswitch to control bacterial cell wall biosynthesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006102-04
Application #
8939869
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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
Miao, Zhichao; Adamiak, Ryszard W; Antczak, Maciej et al. (2017) RNA-Puzzles Round III: 3D RNA structure prediction of five riboswitches and one ribozyme. RNA 23:655-672
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
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
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:
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
Ferré-D'Amaré, Adrian R (2015) On the shoulders of giants. RNA 21:504-5

Showing the most recent 10 out of 29 publications