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Nucleic Acids Res. 2015 Dec 2;43(21):10168-79. doi: 10.1093/nar/gkv1039. Epub 2015 Oct 17.

Full-length RNA structure prediction of the HIV-1 genome reveals a conserved core domain.

Author information

1
BiRC, Bioinformatics Research Centre, Aarhus University, DK-8000 Aarhus C, Denmark zsuzsanna.etches@qiagen.com.
2
iNANO, Interdisciplinary Nanoscience Center, Aarhus University, DK-8000 Aarhus C, Denmark.
3
RTH, Center for non-coding RNA in Technology and Health, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark.
4
BiRC, Bioinformatics Research Centre, Aarhus University, DK-8000 Aarhus C, Denmark.
5
iNANO, Interdisciplinary Nanoscience Center, Aarhus University, DK-8000 Aarhus C, Denmark jk@mb.au.dk.

Abstract

A distance constrained secondary structural model of the ≈10 kb RNA genome of the HIV-1 has been predicted but higher-order structures, involving long distance interactions, are currently unknown. We present the first global RNA secondary structure model for the HIV-1 genome, which integrates both comparative structure analysis and information from experimental data in a full-length prediction without distance constraints. Besides recovering known structural elements, we predict several novel structural elements that are conserved in HIV-1 evolution. Our results also indicate that the structure of the HIV-1 genome is highly variable in most regions, with a limited number of stable and conserved RNA secondary structures. Most interesting, a set of long distance interactions form a core organizing structure (COS) that organize the genome into three major structural domains. Despite overlapping protein-coding regions the COS is supported by a particular high frequency of compensatory base changes, suggesting functional importance for this element. This new structural element potentially organizes the whole genome into three major domains protruding from a conserved core structure with potential roles in replication and evolution for the virus.

PMID:
26476446
PMCID:
PMC4666355
DOI:
10.1093/nar/gkv1039
[Indexed for MEDLINE]
Free PMC Article

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