title: A revised secondary structure model for the 3'-end of hepatitis B virus pregenomic RNA.
abstract: The polymerase encoded by human hepatitis B virus, which has reverse transcriptase and RNase H activity, binds to its pregenomic RNA template in a two-step process involving a terminal redundancy. Both first strand and second strand DNA synthesis involve primer translocation and second strand synthesis involves a template jump. Three parts of the genome, including the so-called core promoter, are known to show deletions in strains usually arising after long-standing HBV infection, but also in some patients treated with interferon. A computer-based study of RNA template folding in the core promoter region, accommodating well-known point mutations, has generated a model for the 3' DR1 primer binding site as being part of a superstructure encompassing an already well-established stem-loop. Depending on the identity of nucleotides 1762 and 1764, the DR1 region may assume two alternative secondary structures which stabilize it as a primer binding site to different extents. Remarkably, one of these structures includes a pronounced loop which coincides with at least 12 related deletions seen in HBV DNA from different patients. Thus according to the model, the 5'- and 3'-ends of pregenomic RNA, which share primary sequences but have separate functions, are not structural equivalents. An RNA superstructure near the 3'-end of all HBV transcripts could have far-reaching implications for the modulation of both genome replication and post-transcriptional processing.
authors.affiliation: Department of Virology, University of Umeå, Sweden.
authors.forename: A H
authors.initials: AH
authors.lastname: Kidd
authors.forename: K
authors.initials: K
authors.lastname: Kidd-Ljunggren
mesh_terms: D001483:Base Sequence; D003198:Computer Simulation; D004279:DNA, Viral / Q000235:genetics; D014644:Genetic Variation; D016679:Genome, Viral; D006509:Hepatitis B / Q000821:virology; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D012367:RNA, Viral; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein