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

TY - JOUR

T1 - Full-length RNA structure prediction of the HIV-1 genome reveals a conserved core domain

AU - Sükösd, Zsuzsanna

AU - Andersen, Ebbe Sloth

AU - Seemann, Ernst Stefan

AU - Jensen, Mads Krogh

AU - Hansen, Mathias

AU - Gorodkin, Jan

AU - Kjems, Jørgen

N1 - © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2015/12/2

Y1 - 2015/12/2

N2 - 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.

AB - 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.

U2 - 10.1093/nar/gkv1039

DO - 10.1093/nar/gkv1039

M3 - Journal article

C2 - 26476446

SN - 0305-1048

VL - 43

SP - 10168

EP - 10179

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 21

ER -