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Metabolite Recognition Principles and Molecular Mechanisms Underlying Riboswitch Function
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Riboswitches are mRNA elements capable of modulating gene expression in response to specific binding by cellular metabolites. Riboswitches exert their function through the interplay of alternative ligand-free and ligand-bound conformations of the metabolite-sensing domain, which in turn modulate the formation of adjacent gene expression controlling elements. X-ray crystallography and NMR spectroscopy have determined three-dimensional structures of virtually all the major riboswitch classes in the ligand-bound state and, for several riboswitches, in the ligand-free state. The resulting spatial topologies have demonstrated the wide diversity of riboswitch folds and revealed structural principles for specific recognition by cognate metabolites. The available three-dimensional information, supplemented by structure-guided biophysical and biochemical experimentation, has led to an improved understanding of how riboswitches fold, what RNA conformations are required for ligand recognition, and how ligand binding can be transduced into gene expression modulation. These studies have greatly facilitated the dissection of molecular mechanisms underlying riboswitch action and should in turn guide the anticipated development of tools for manipulating gene regulatory circuits.
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“It seems interesting to note that, although direct recognition of amino acids by RNA molecules seems to be banished from the modern translation system, it survives in other functional spheres of modern cells, in particular, as amino acid-binding riboswitches [96,97].”
From Frozen Accident Pushing 50: Stereochemistry, Expansion, and Chance in the Evolution of the Genetic Code (2017) · cites this paper as [97]
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Xu, L., Xiao, Y., Zhang, J., & Fang, X. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkac1257 · Cited by 10
Metadata
- Authors
- Serganov, A., & Patel, D. J.
- Affiliations
- New York University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- Annual Review of Biophysics
- Publisher
- Annual Reviews
- Published
- 2012-06-09
- Volume
- 41
- Issue
- 1
- Pages
- 343-370
- ISSN
- 1936-122X (ISSN-L)
- 1936-1238
- PMC
- PMC4696762
- OpenAlex
- W2129215648
- Cited by
- 160
- References
- 136
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 6 · 2020: 13 · 2019: 12 · 2018: 9 · 2017: 10 · 2016: 13 · 2015: 24 · 2014: 27 · 2013: 9 · 2012: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- National Institute of General Medical Sciences (P41GM066354, GM 66354, R01GM034504)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- riboswitches, ligand binding, RNA conformational change, gene expression regulation, RNA folding, ligand-free state, ligand-bound state, riboswitch structure, RNA-ligand interactions, gene regulatory circuits
- MeSH terms
- Bacteria, Ligands, Nucleic Acid Conformation, RNA, Messenger, Gene Expression Regulation, Bacterial, Crystallography, X-Ray, Riboswitch
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