RNA interactions in the 5′ region of the HIV-1 genome

被引:98
作者
Damgaard, CK
Andersen, ES
Knudsen, B
Gorodkin, J
Kjems, J
机构
[1] Aarhus Univ, Dept Mol Biol, DK-8000 Aarhus, Denmark
[2] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus, Denmark
[3] Royal Vet & Agr Univ, Div Anim Genet, Inst Anim Sci & Anim Hlth, DK-1870 Frederiksberg, Denmark
关键词
HIV-1; RNA structure; conformation; 5 ' UTR; UV-crosslinking;
D O I
10.1016/j.jmb.2003.12.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The untranslated leader of the dimeric HIV-1 RNA genome is folded into a complex structure that plays multiple and essential roles in the viral replication cycle. Here, we have investigated secondary and tertiary structural elements within the 5' 744 nucleotides of the HIV-1 genome using a combination of bioinformatics, enzymatic probing, native gel electrophoresis, and UV-crosslinking experiments. We used a recently developed RNA folding algorithm (Pfold) to predict the common secondary structure of an alignment of 20 divergent HIV-1 sequences. Combining this analysis with biochemical data, we present a secondary structure model for the entire 744 nucleotide fragment, which incorporates previously recognized and novel structural elements. In particular, our data provided strong evidence for a long-distance interaction between the region encompassing the AUG Gag initiation codon and an upstream region and we demonstrate that this feature is highly conserved in distantly related human and animal retroviruses. To obtain information about tertiary interactions we applied an intramolecular UV-crosslinking strategy and identified a novel tertiary interaction within the PBS hairpin structure. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:369 / 379
页数:11
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