Riboswitches that sense <i>S</i>-adenosylmethionine and <i>S</i>-adenosylhomocysteineThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Systems and Chemical Biology, and has undergone the Journal's usual peer review process.

  • Joy Xin Wang
    Department of Molecular, Cellular and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA.
  • Ronald R. Breaker
    Department of Molecular, Cellular and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA.

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<jats:p> Numerous riboswitches have been discovered that specifically recognize metabolites and modulate gene expression. Each riboswitch class is defined either by the consensus sequence and structural features of its metabolite-binding aptamer domain, or by the distinct metabolite that the aptamer recognizes. Several distinct classes of riboswitches that respond to S-adenosylmethionine (SAM or AdoMet) have been discovered. Representatives of these classes have been shown to strongly discriminate against S-adenosylhomocystenine (SAH or AdoHcy), which is the metabolic byproduct produced when SAM is used as a cofactor for methylation reactions. However, a distinct class of riboswitches that selectively binds SAH, and strongly discriminates against SAM, also has been discovered. Herein we compare the features of SAM and SAH riboswitches, which help showcase the enormous structural diversity that RNA can harness to form precision genetic switches for compounds that are critical for fundamental metabolic processes. </jats:p>

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