title: The frameshift signal of HIV-1 involves a potential intramolecular triplex RNA structure.
abstract: The cis-acting mRNA elements that promote programmed -1 ribosomal frameshifting present a natural target for the rational design of antiretroviral chemotherapies. It has been commonly accepted that the HIV-1 frameshifting signal is special, because its downstream enhancer element consists of a simple mRNA stem loop rather than a more complex secondary structure such as a pseudoknot. Here we present three lines of evidence, bioinformatic, structural, and genetic, showing that the biologically relevant HIV-1 frameshift signal contains a complex RNA structure that likely includes an extended RNA triple-helix region. We suggest that the potential intramolecular triplex structure is essential for viral propagation and viability, and that small molecules targeted to this RNA structure may possess antiretroviral activities.
authors.affiliation: Department of Cell Biology and Molecular Genetics, 2135 Microbiology Building, University of Maryland, College Park, MD 20742, USA. jd280@umail.umd.edu
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Dinman
authors.forename: Sara
authors.initials: S
authors.lastname: Richter
authors.forename: Ewan P
authors.initials: EP
authors.lastname: Plant
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Taylor
authors.forename: Amy B
authors.initials: AB
authors.lastname: Hammell
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D001483:Base Sequence; D004247:DNA; D019992:Databases as Topic; D016368:Frameshift Mutation; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D012333:RNA, Messenger; C051802:triplex DNA; D012313:RNA; D004247:DNA; D012260:Ribonucleases