A structural intermediate pre-organizes the add adenine riboswitch for ligand recognition
Abstract
Riboswitches are RNA sequences that regulate gene expression by undergoing structural changes upon the specific binding of cellular metabolites. Crystal structures of purine-sensing riboswitches have revealed an intricate network of interactions surrounding the ligand in the bound complex. The mechanistic details about how the aptamer folding pathway is involved in the formation of the metabolite binding site have been previously shown to be highly important for the riboswitch regulatory activity. Here, a combination of single-molecule FRET and SHAPE assays have been used to characterize the folding pathway of the adenine riboswitch from Vibrio vulnificus. Experimental evidences suggest a folding process characterized by the presence of a structural intermediate involved in ligand recognition. This intermediate state acts as an open conformation to ensure ligand accessibility to the aptamer and folds into a structure nearly identical to the ligand-bound complex through a series of structural changes. This study demonstrates that the add riboswitch relies on the folding of a structural intermediate that preorganizes the aptamer global structure and the ligand binding site to allow efficient metabolite sensing and riboswitch genetic regulation.
Citation
St-Pierre , P , Shaw , E S , Jacques , S , Dalgarno , P A , Perez Gonzalez , C , Picard-Jean , F , Penedo , C & Lafontaine , D A 2021 , ' A structural intermediate pre-organizes the add adenine riboswitch for ligand recognition ' , Nucleic Acids Research , vol. Advance Article . https://doi.org/10.1093/nar/gkab307
Publication
Nucleic Acids Research
Status
Peer reviewed
ISSN
0305-1048Type
Journal article
Description
Funding: This work was supported by the National Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Institutes of Health Research (CIHR). P.S.P. was supported through a Doctoral fellowship from NSERC and D.A.L was supported through a Fonds de Recherche Santé Québec Senior scholarship. C. Perez-Gonzalez and E. Shaw thank the Engineering and Physical Sciences Research Council (EPSRC) and The University of St Andrews for PhD studentships.Collections
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.