Tertiary contacts control switching of the SAM-I riboswitch
Abstract
Riboswitches are non-coding RNAs that control gene expression by sensing small molecules through changes in secondary structure. While secondary structure and ligand interactions are thought to control switching, the exact mechanism of control is unknown. Using a novel two-piece assay that competes the anti-terminator against the aptamer, we directly monitor the process of switching. We find that the stabilization of key tertiary contacts controls both aptamer domain collapse and the switching of the SAM-I riboswitch from the aptamer to the expression platform conformation. Our experiments demonstrate that SAM binding induces structural alterations that indirectly stabilize the aptamer domain, preventing switching toward the expression platform conformer. These results, combined with a variety of structural probing experiments performed in this study, show that the collapse and stabilization of the aptamer domain are cooperative, relying on the sum of key tertiary contacts and the bimodal stability of the kink-turn motif for function. Here, ligand binding serves to shift the equilibrium of aptamer domain structures from a more open toward a more stable collapsed form by stabilizing tertiary interactions. Our data show that the thermodynamic landscape for riboswitch operation is finely balanced to allow large conformational rearrangements to be controlled by small molecule interactions.
- Authors:
-
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Div. Theoretical Biology and Biophysics
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- OSTI Identifier:
- 1625472
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nucleic Acids Research
- Additional Journal Information:
- Journal Volume: 39; Journal Issue: 6; Journal ID: ISSN 0305-1048
- Publisher:
- Oxford University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Biochemistry & Molecular Biology
Citation Formats
Hennelly, Scott P., and Sanbonmatsu, Karissa Y. Tertiary contacts control switching of the SAM-I riboswitch. United States: N. p., 2010.
Web. doi:10.1093/nar/gkq1096.
Hennelly, Scott P., & Sanbonmatsu, Karissa Y. Tertiary contacts control switching of the SAM-I riboswitch. United States. https://doi.org/10.1093/nar/gkq1096
Hennelly, Scott P., and Sanbonmatsu, Karissa Y. Fri .
"Tertiary contacts control switching of the SAM-I riboswitch". United States. https://doi.org/10.1093/nar/gkq1096. https://www.osti.gov/servlets/purl/1625472.
@article{osti_1625472,
title = {Tertiary contacts control switching of the SAM-I riboswitch},
author = {Hennelly, Scott P. and Sanbonmatsu, Karissa Y.},
abstractNote = {Riboswitches are non-coding RNAs that control gene expression by sensing small molecules through changes in secondary structure. While secondary structure and ligand interactions are thought to control switching, the exact mechanism of control is unknown. Using a novel two-piece assay that competes the anti-terminator against the aptamer, we directly monitor the process of switching. We find that the stabilization of key tertiary contacts controls both aptamer domain collapse and the switching of the SAM-I riboswitch from the aptamer to the expression platform conformation. Our experiments demonstrate that SAM binding induces structural alterations that indirectly stabilize the aptamer domain, preventing switching toward the expression platform conformer. These results, combined with a variety of structural probing experiments performed in this study, show that the collapse and stabilization of the aptamer domain are cooperative, relying on the sum of key tertiary contacts and the bimodal stability of the kink-turn motif for function. Here, ligand binding serves to shift the equilibrium of aptamer domain structures from a more open toward a more stable collapsed form by stabilizing tertiary interactions. Our data show that the thermodynamic landscape for riboswitch operation is finely balanced to allow large conformational rearrangements to be controlled by small molecule interactions.},
doi = {10.1093/nar/gkq1096},
journal = {Nucleic Acids Research},
number = 6,
volume = 39,
place = {United States},
year = {Fri Nov 19 00:00:00 EST 2010},
month = {Fri Nov 19 00:00:00 EST 2010}
}
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An mRNA structure in bacteria that controls gene expression by binding lysine
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A loop loop interaction and a K-turn motif located in the lysine aptamer domain are important for the riboswitch gene regulation control
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Ligand-induced folding of the guanine-sensing riboswitch is controlled by a combined predetermined induced fit mechanism
journal, September 2007
- Ottink, O. M.; Rampersad, S. M.; Tessari, M.
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