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• W2034345982 endingPage "349" @default.
• W2034345982 startingPage "331" @default.
• W2034345982 abstract "Riboswitches are promising targets for the design of novel antibiotics and engineering of portable genetic regulatory elements. There is evidence that variability in riboswitch properties allows tuning of expression for genes involved in different stages of biosynthetic pathways by mechanisms that are not currently understood. Here, we explore the mechanism for tuning of S-adenosyl methionine (SAM)-I riboswitch folding. Most SAM-I riboswitches function at the transcriptional level by sensing the cognate ligand SAM. SAM-I riboswitches orchestrate the biosynthetic pathways of cysteine, methionine, SAM, and so forth. We use base-pair probability predictions to examine the secondary-structure folding landscape of several SAM-I riboswitch sequences. We predict different folding behaviors for different SAM-I riboswitch sequences. We identify several decoy base-pairing interactions involving 5' riboswitch residues that can compete with the formation of a P1 helix, a component of the ligand-bound transcription OFF state, in the absence of SAM. We hypothesize that blockage of these interactions through SAM contacts contributes to stabilization of the OFF state in the presence of ligand. We also probe folding patterns for a SAM-I riboswitch RNA using constructs with different 3' truncation points experimentally. Folding was monitored through fluorescence, susceptibility to base-catalyzed cleavage, nuclear magnetic resonance, and indirectly through SAM binding. We identify key decision windows at which SAM can affect the folding pathway towards the OFF state. The presence of decoy conformations and differential sensitivities to SAM at different transcript lengths is crucial for SAM-I riboswitches to modulate gene expression in the context of global cellular metabolism." @default.
• W2034345982 created "2016-06-24" @default.
• W2034345982 creator A5007996238 @default.
• W2034345982 creator A5022470629 @default.
• W2034345982 creator A5038763846 @default.
• W2034345982 creator A5072597347 @default.
• W2034345982 date "2012-05-01" @default.
• W2034345982 modified "2023-09-28" @default.
• W2034345982 title "Conformational Heterogeneity of the SAM-I Riboswitch Transcriptional ON State: A Chaperone-Like Role for S-Adenosyl Methionine" @default.
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• W2034345982 doi "https://doi.org/10.1016/j.jmb.2012.02.019" @default.
• W2034345982 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4767528" @default.
• W2034345982 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22425639" @default.
• W2034345982 hasPublicationYear "2012" @default.

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