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J. Biol. Chem., Vol. 278, Issue 8, 5685-5693, February 21, 2003
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From the Institute of Molecular Biology, Academia Sinica,
Taipei 11529, Taiwan, Republic of China
We have previously shown that the N-terminal
domain of hepatitis delta virus (NdAg) has an RNA chaperone activity
in vitro (Huang, Z. S., and Wu, H. N. (1998)
J. Biol. Chem. 273, 26455-26461). Here we investigate
further the basis of the stimulatory effect of NdAg on RNA structural
rearrangement: mainly the formation and breakage of base pairs. Duplex
dissociation, strand annealing, and exchange of complementary RNA
oligonucleotides; the hybridization of yeast U4 and U6 small nuclear
RNAs and of hammerhead ribozymes and cognate substrates; and the
cis-cleavage reaction of hepatitis delta ribozymes were used to
determine directly the role of NdAg in RNA-mediated processes. The
results showed that NdAg could accelerate the annealing of
complementary sequences in a selective fashion and promote strand
exchange for the formation of a more extended duplex. These activities
would prohibit NdAg from modifying the structure of a stable RNA, but
allow NdAg to facilitate a trans-acting hammerhead ribozyme to find a
more extensively matched target in cognate substrate. These and other
results suggest that hepatitis delta antigen may have a biological role
as an RNA chaperone, modulating the folding of viral RNA for
replication and transcription.
Selective Strand Annealing and Selective Strand Exchange Promoted
by the N-terminal Domain of Hepatitis Delta Antigen*
*
This work was supported by the Academia Sinica (Republic of
China) and by Grants NSC-89-2311-B-001-077 and NSC-90-2311-B-001-013 from the National Science Council (Republic of China).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 886-2-27883134;
Fax: 886-2-27826085; E-mail: hnwu@gate.sinica.edu.tw.
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