Nucleic Acids Research, Vol 24, Issue 17 3295-3301, Copyright © 1996 by Oxford University Press
AH Kidd and K Kidd-Ljunggren
The polymerase encoded by human hepatitis B virus, which has reverse
transcriptase and RNase H activity, binds to its pregenomic RNA template in
a two-step process involving a terminal redundancy. Both first strand and
second strand DNA synthesis involve primer translocation and second strand
synthesis involves a template jump. Three parts of the genome, including
the so-called core promoter, are known to show deletions in strains usually
arising after long-standing HBV infection, but also in some patients
treated with interferon. A computer-based study of RNA template folding in
the core promoter region, accommodating well-known point mutations, has
generated a model for the 3' DR1 primer binding site as being part of a
superstructure encompassing an already well-established stem-loop.
Depending on the identity of nucleotides 1762 and 1764, the DR1 region may
assume two alternative secondary structures which stabilize it as a primer
binding site to different extents. Remarkably, one of these structures
includes a pronounced loop which coincides with at least 12 related
deletions seen in HBV DNA from different patients. Thus according to the
model, the 5'- and 3'-ends of pregenomic RNA, which share primary sequences
but have separate functions, are not structural equivalents. An RNA
superstructure near the 3'-end of all HBV transcripts could have far-
reaching implications for the modulation of both genome replication and
post-transcriptional processing.
ARTICLES
A revised secondary structure model for the 3'-end of hepatitis B virus pregenomic RNA
Department of Virology, University of Umea, Sweden.
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