cis rescue of a mutated reverse transcriptase gene of human hepatitis B virus by creation of an internal ATG.
Using mutational analysis, we have investigated the translation strategy of the reverse transcriptase gene (pol) of human hepatitis B virus. It has been proposed that this pol gene product is synthesized as a core-pol fusion protein from a polycistronic mRNA template via ribosomal frameshifting, a mechanism often seen in retroelements. Our data indicate that creation of a novel ATG initiation codon near the original ATG can compensate for a lethal missense mutation at the first ATG position of the pol open reading frame. Genetic analysis has rigorously ruled out the possibilities of frameshifting, non-ATG initiation, or RNA editing. These results are discussed in the context of a 5'-end entry model versus a novel model of direct internal entry of ribosomes.
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia 19104-6059.
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Roychoudhury
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Shih
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D005796:Genes; D005804:Genes, Lethal; D005814:Genes, Viral; D005822:Genetic Vectors; D006515:Hepatitis B virus / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D013698:Templates, Genetic; D014158:Transcription, Genetic; D014162:Transfection; D015678:Viral Structural Proteins / Q000235:genetics*
D004279:DNA, Viral; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D015678:Viral Structural Proteins; D012194:RNA-Directed DNA Polymerase