Riboswitches that sense S-adenosylhomocysteine and activate genes involved in coenzyme recycling.
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.
Wang
Joy Xin
JX
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Lee
Elaine R
ER
Morales
Dianali Rivera
DR
Lim
Jinsoo
J
Breaker
Ronald R
RR
D020121:5' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D003067:Coenzymes / Q000378:metabolism*; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D006710:Homocysteine / Q000378:metabolism; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000235:genetics*; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism
D020121:5' Untranslated Regions; D003067:Coenzymes; D012329:RNA, Bacterial; D006710:Homocysteine; D012313:RNA; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine