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A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA

Abstract

HEPATITIS delta virus genomic and antigenomic RNAs contain a self-cleavage site hypothesized to function in processing the viral RNA during replication1–3. Self-cleavage requires only a divalent cation1–3 and is mediated at the genomic site by a sequence of less than 85 nucleotides4. We propose that the genomic self-cleaving sequence element4 and a corresponding sequence from the anti-genomic RNA could generate related secondary structures. The region of the antigenomic sequence, predicted from the proposed structure, was synthesized and shown to be sufficient for self-cleavage. Evidence for two stems which form a tertiary interaction was obtained by site-specific mutagenesis of the antigenomic sequence. Efficient self-cleavage in 10 M formamide or 5 M urea, also a property of the genomic sequence5, was dependent on base-pairing in both stems. But in the absence of denaturants, the stem distal to the site of cleavage was not required, suggesting that the tertiary interaction stabilizes the structure required for self-cleavage.

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Perrotta, A., Been, M. A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA. Nature 350, 434–436 (1991). https://doi.org/10.1038/350434a0

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