Riboswitches that sense S-adenosylhomocysteine and activate genes involved in coenzyme recycling

Mol Cell. 2008 Mar 28;29(6):691-702. doi: 10.1016/j.molcel.2008.01.012.


We have identified a highly conserved RNA motif that occurs upstream of genes involved in S-adenosyl-L-methionine (SAM) recycling in many Gram-positive and Gram-negative species of bacteria. The phylogenetic distribution and the conserved structural features of representatives of this motif are indicative of riboswitch function. Riboswitches are widespread metabolite-sensing gene control elements that are typically found in the 5' untranslated regions (UTRs) of bacterial mRNAs. We experimentally verified that examples of this RNA motif specifically recognize S-adenosylhomocysteine (SAH) in protein-free in vitro assays, and confirmed that these RNAs strongly discriminate against SAM and other closely related analogs. A representative SAH motif was found to activate expression of a downstream gene in vivo when the metabolite is bound. These observations confirm that SAH motif RNAs are distinct ligand-binding aptamers for a riboswitch class that selectively binds SAH and controls genes essential for recycling expended SAM coenzymes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • 5' Untranslated Regions / metabolism
  • Base Sequence
  • Binding Sites
  • Coenzymes / metabolism*
  • Conserved Sequence
  • Gene Expression Regulation*
  • Homocysteine / metabolism
  • Kinetics
  • Methionine / metabolism
  • Nucleic Acid Conformation
  • RNA / chemistry
  • RNA / genetics*
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism
  • S-Adenosylhomocysteine / metabolism*
  • S-Adenosylmethionine / metabolism


  • 5' Untranslated Regions
  • Coenzymes
  • RNA, Bacterial
  • Homocysteine
  • RNA
  • S-Adenosylmethionine
  • S-Adenosylhomocysteine
  • Methionine