title: Ligand-responsive RNA mechanical switches.
abstract: Ligand-responsive RNA mechanical switches represent a new class of simple switching modules that adopt well-defined ligand-free and bound conformational states, distinguishing them from metabolite-sensing riboswitches. Initially discovered in the internal ribosome entry site (IRES) of hepatitis C virus (HCV), these RNA switch motifs were found in the genome of diverse other viruses. Although large variations are seen in sequence and local secondary structure of the switches, their function in viral translation initiation that requires selective ligand recognition is conserved. We recently determined the crystal structure of an RNA switch from Seneca Valley virus (SVV) which is able to functionally replace the switch of HCV. The switches from both viruses recognize identical cognate ligands despite their sequence dissimilarity. Here, we describe the discovery of 7 new switches in addition to the previously established 5 examples. We highlight structural and functional features unique to this class of ligand-responsive RNA mechanical switches and discuss implications for therapeutic development and the construction of RNA nanostructures.
authors.affiliation: a Department of Chemistry and Biochemistry ; University of California, San Diego ; La Jolla , CA USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Boerneke
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermann
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics; D008024:Ligands; D008957:Models, Genetic; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010849:Picornaviridae / Q000235:genetics; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D058928:Riboswitch
chemical_list: D008024:Ligands; D012367:RNA, Viral; D058928:Riboswitch; D012313:RNA
keywords: AEV, avian encephalomyelitis virus; BDV, border disease virus; BVDV, bovine viral diarrhea virus; CSFV, classical swine fever virus; DHV, Duck hepatitis virus; DPV, duck picornavirus; GBV, GB virus; GPV, giraffe pestivirus; HCV, hepatitis C virus; IRES; IRES, internal ribosome entry site; IVT, in vitro translation; NPHV, non-primate hepacivirus; RNA switch; SPV, simian picornavirus; SVV, Seneca Valley virus; conformational switch; hepatitis C virus; riboswitch