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Catalytic RNAs

Gene regulatory RNAs

RNA in signal transduction

RNA-protein interactions

RNA analogs of GFP

Small molecule recognition by RNA

RNA folding and dynamics

Molecular evolution

Methods

 

Ferré-D'Amaré Lab Research > RNA in signal transduction

Riboswitches sense the intracellular concentration of small molecules and respond by altering transcription, translation or splicing of specific groups of genes. Of particular interest are bacterial riboswitches that respond to the concentration of intracellular signals (second messengers) such as c-di-AMP, c-di-GMP, and ZMP. These second messengers are broadly employed by bacteria to respond to extracellular insults, to control changes in lifestyle (e.g., from motile or planktonic to sessile) and to address imbalances in intermediate metabolism. The second messenger c-di-GMP (cyclic diguanylate) is critical for biofilm formation. Biofilms are typically refractory to antibiotics and other bactericidal and bacteriostatic interventions, and because they colonize most medical devices, are a major cause of human morbidity and mortality in clinical settings. C-di-GMP riboswitches control a diverse set of genes in many pathogenic bacteria. Our study of these riboswitches is important for understanding the signaling pathways that lead to bacterial adaptation, virulence, and the mammalian immune response, and may lead to riboswitch-targeted strategies to overcome bacterial infections.

• Jones, C.P. & Ferré-D'Amaré, A.R. Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains. Nature Struct. Mol. Biol. 22, 679-685 (2015). [abstract]

• Baird, N.J., Inglese, J., & Ferré-D'Amaré, A.R. Rapid RNA-ligand interaction analysis through high-information content conformational and stability landscapes. Nature Comm. 6, 8898 (2015). [abstract]

• Jones, C.P., & Ferré-D'Amaré, A.R. Crystal structure of a c-di-AMP riboswitch reveals an internally pseudo-dimeric RNA. EMBO J. 33, 2692-2703 (2014). [abstract]

• Wood, S., Ferré-D'Amaré, A.R. & Rueda, D. Allosteric tertiary interactions pre-organize the c-di-GMP riboswitch and accelerate ligand binding. ACS Chem. Biol. 7, 920-927 (2012). [abstract]

• Kulshina, N., Baird, N.J., & Ferré-D'Amaré, A.R. Recognition of the bacterial second messenger cyclic diguanylate by its cognate riboswitch. Nature Struct. Mol. Biol. 16, 1212-1217 (2009). [abstract]