title: On the role of four small hairpins in the HIV-1 RNA genome.
abstract: An RNA secondary structure model for the complete HIV-1 genome has recently been published based on SHAPE technology. Several well-known RNA motifs such as TAR and RRE were confirmed and numerous new structured motifs were described that may play important roles in virus replication. The 9 kb viral RNA genome is densely packed with many RNA hairpin motifs and the collective fold may play an important role in HIV-1 biology. We initially focused on 16 RNA hairpin motifs scattered along the viral genome. We considered conservation of these structures, despite sequence variation among virus isolates, as a first indication for a significant function. Four relatively small hairpins exhibited considerable structural conservation and were selected for experimental validation in virus replication assays. Mutations were introduced into the HIV-1 RNA genome to destabilize individual RNA structures without affecting the protein-coding properties (silent codon changes). No major virus replication defects were scored, suggesting that these four hairpin structures do not play essential roles in HIV-1 replication.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center; University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Stefanie A
authors.initials: SA
authors.lastname: Knoepfel
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
mesh_terms: D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D010802:Phylogeny; D059370:RNA Folding; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics; D014779:Virus Replication
chemical_list: D034741:RNA, Small Interfering; D012367:RNA, Viral
keywords: HIV-1; RNA; RNA structure; SHAPE; hairpin
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