Selective strand annealing and selective strand exchange promoted by the N-terminal domain of hepatitis delta antigen.
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.
Huang
Zhi-Shun
ZS
Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of China.
Su
Wen-Huey
WH
Wang
Jui-Ling
JL
Wu
Huey-Nan
HN
D001483:Base Sequence; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000737:chemistry*; D004926:Escherichia coli / Q000235:genetics; D003698:Hepatitis Delta Virus / Q000502:physiology*; D035923:Hepatitis delta Antigens / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010446:Peptide Fragments / Q000494:pharmacology*; D016337:RNA, Catalytic / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013379:Substrate Specificity
D004279:DNA, Viral; D035923:Hepatitis delta Antigens; D010446:Peptide Fragments; D016337:RNA, Catalytic; D012342:RNA, Small Nuclear; D012367:RNA, Viral; C427204:hammerhead ribozyme