title: Functional conservation despite structural divergence in ligand-responsive RNA switches.
abstract: An internal ribosome entry site (IRES) initiates protein synthesis in RNA viruses, including the hepatitis C virus (HCV). We have discovered ligand-responsive conformational switches in viral IRES elements. Modular RNA motifs of greatly distinct sequence and local secondary structure have been found to serve as functionally conserved switches involved in viral IRES-driven translation and may be captured by identical cognate ligands. The RNA motifs described here constitute a new paradigm for ligand-captured switches that differ from metabolite-sensing riboswitches with regard to their small size, as well as the intrinsic stability and structural definition of the constitutive conformational states. These viral RNA modules represent the simplest form of ligand-responsive mechanical switches in nucleic acids.
authors.affiliation: Department of Chemistry and Biochemistry.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Boerneke
authors.affiliation: Department of Chemistry and Biochemistry.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Dibrov
authors.affiliation: Department of Chemistry and Biochemistry.
authors.forename: Jing
authors.initials: J
authors.lastname: Gu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, and.
authors.forename: David L
authors.initials: DL
authors.lastname: Wyles
authors.affiliation: Department of Chemistry and Biochemistry, Center for Drug Discovery Innovation, University of California, San Diego, La Jolla, CA 92093 tch@ucsd.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermann
mesh_terms: D002474:Cell-Free System / Q000737:chemistry / Q000378:metabolism; D016174:Hepacivirus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis / Q000502:physiology; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D012367:RNA, Viral; D038621:Regulatory Sequences, Ribonucleic Acid; D014764:Viral Proteins
keywords: IRES elements; RNA viruses; hepatitis C virus; translation regulation