Structure of the S-adenosylmethionine riboswitch regulatory mRNA element

Nature. 2006 Jun 29;441(7097):1172-5. doi: 10.1038/nature04819.


Riboswitches are cis-acting genetic regulatory elements found in the 5'-untranslated regions of messenger RNAs that control gene expression through their ability to bind small molecule metabolites directly. Regulation occurs through the interplay of two domains of the RNA: an aptamer domain that responds to intracellular metabolite concentrations and an expression platform that uses two mutually exclusive secondary structures to direct a decision-making process. In Gram-positive bacteria such as Bacillus species, riboswitches control the expression of more than 2% of all genes through their ability to respond to a diverse set of metabolites including amino acids, nucleobases and protein cofactors. Here we report the 2.9-angstroms resolution crystal structure of an S-adenosylmethionine (SAM)-responsive riboswitch from Thermoanaerobacter tengcongensis complexed with S-adenosylmethionine, an RNA element that controls the expression of several genes involved in sulphur and methionine metabolism. This RNA folds into a complex three-dimensional architecture that recognizes almost every functional group of the ligand through a combination of direct and indirect readout mechanisms. Ligand binding induces the formation of a series of tertiary interactions with one of the helices, serving as a communication link between the aptamer and expression platform domains.

Publication types

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

MeSH terms

  • Azoarcus / genetics
  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Gene Expression Regulation, Bacterial / drug effects
  • Introns / genetics
  • Ligands
  • Methionine / metabolism
  • Models, Molecular
  • Nucleic Acid Conformation*
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism
  • RNA, Messenger / chemistry*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • S-Adenosylmethionine / chemistry
  • S-Adenosylmethionine / metabolism*
  • S-Adenosylmethionine / pharmacology*
  • Static Electricity
  • Sulfur / metabolism
  • Thermoanaerobacter / chemistry*
  • Thermoanaerobacter / genetics*
  • Thermoanaerobacter / metabolism


  • Ligands
  • RNA, Bacterial
  • RNA, Messenger
  • Sulfur
  • S-Adenosylmethionine
  • Methionine

Associated data

  • PDB/2GIS