Bioinformatic analysis of riboswitch structures uncovers variant classes with altered ligand specificity

Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):E2077-E2085. doi: 10.1073/pnas.1619581114. Epub 2017 Mar 6.


Riboswitches are RNAs that form complex, folded structures that selectively bind small molecules or ions. As with certain groups of protein enzymes and receptors, some riboswitch classes have evolved to change their ligand specificity. We developed a procedure to systematically analyze known riboswitch classes to find additional variants that have altered their ligand specificity. This approach uses multiple-sequence alignments, atomic-resolution structural information, and riboswitch gene associations. Among the discoveries are unique variants of the guanine riboswitch class that most tightly bind the nucleoside 2'-deoxyguanosine. In addition, we identified variants of the glycine riboswitch class that no longer recognize this amino acid, additional members of a rare flavin mononucleotide (FMN) variant class, and also variants of c-di-GMP-I and -II riboswitches that might recognize different bacterial signaling molecules. These findings further reveal the diverse molecular sensing capabilities of RNA, which highlights the potential for discovering a large number of additional natural riboswitch classes.

Keywords: 2′-deoxyguanosine; aptamer; c-di-GMP; glycine; guanine.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites
  • Computational Biology / methods*
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism
  • Deoxyguanosine / chemistry
  • Glycine / chemistry
  • Guanine / chemistry
  • Ligands
  • Models, Molecular
  • Nucleic Acid Conformation
  • RNA / chemistry*
  • RNA / genetics*
  • Riboswitch / genetics*


  • Ligands
  • Riboswitch
  • Guanine
  • bis(3',5')-cyclic diguanylic acid
  • RNA
  • Deoxyguanosine
  • Cyclic GMP
  • Glycine