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A Host-Specific Function Is Required for Ligation of a Wide Variety of Ribozyme-Processed RNAs

Carl E. Reid and David W. Lazinski
Proceedings of the National Academy of Sciences of the United States of America
Vol. 97, No. 1 (Jan. 4, 2000), pp. 424-429
Stable URL: http://www.jstor.org/stable/121806
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
A Host-Specific Function Is Required for Ligation of a Wide Variety of Ribozyme-Processed RNAs
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Abstract

Hepatitis δ virus (HDV) replicates its circular RNA genome via a rolling circle mechanism. During this process, cis-acting ribozymes cleave adjacent upstream sequences and thereby resolve replication intermediates to unit-length RNA. The subsequent ligation of these 5′OH and 2′,3′-cyclic phosphate termini to form circular RNA is an essential step in the life cycle of the virus. Here we present evidence for the involvement of a host activity in the ligation of HDV RNA. We used both HDV and hammerhead ribozymes to generate a panel of HDV and non-HDV RNA substrates that bear 5′-hydroxyl and 2′,3′-cyclic phosphate termini. We found that ligation of these substrates occurred in host cells, but not in vitro or in Escherichia coli. The host-specific ligation activity was capable of joining RNA in both bimolecular and intramolecular reactions and functioned in a sequence-independent manner. We conclude that mammalian cells contain a default pathway that efficiently circularizes ribozyme processed RNAs. This pathway could be exploited in the delivery of stable antisense and decoy RNA to the nucleus.

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