Nucleic Acids Research, Vol 25, Issue 20 4085-4092, Copyright © 1997 by Oxford University Press
TS Wadkins and MD Been
The two ribozymes found in hepatitis delta virus RNA form related but
non-identical secondary structures and display similar cleavage properties
in vitro. Three of the non-duplex elements hypothesized to contribute
nucleotides to the catalytic core vary slightly in length between the two
ribozymes and the differences are conserved in clinical isolates. Possible
functional relationships of the core sequence elements were tested by
systematically exchanging sequences between the two ribozymes. It was found
that switching two of the elements (L3 and J4/2) from one ribozyme to the
other reduced cleavage activity in both. On the other hand, exchanging the
third region (J1/4) resulted in enhanced activity for one ribozyme and a
smaller increase in activity for the other. Combining exchanges did not
reveal any compensatory interactions involving these particular elements
nor did a pattern emerge that would suggest an optimal combination of core
sequences for a generalized HDV ribozyme. Non-compensatory behavior
reinforces the idea that the non-duplex sequences may form
sequence-specific contacts with duplex portions of the ribozyme, but, in
addition, these data suggest that there may be selective pressures on the
ribozyme sequences in the virus that are not reflected in the in vitro
self-cleavage assays.
ARTICLES
Core-associated non-duplex sequences distinguishing the genomic and antigenomic self-cleaving RNAs of hepatitis delta virus
Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
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