Determinants of apical loop–internal loop RNA–RNA interactions involving the HCV IRES

Gomes, Sonia Da Rocha; Dausse, Eric; Toulmé, Jean‐Jacques

doi:10.1016/j.bbrc.2004.07.185

Cited by 35 publications

(29 citation statements)

References 28 publications

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“…ALIL complexes are a type of kissing complex widely distributed in nature, and play important roles in many biological processes (Brunel et al 2002). In vitro-selected RNA aptamers also exploit this strategy to efficiently associate with their targets (Aldaz-Carroll et al 2002;Da Rocha Gomes et al 2004). In all cases, the presence of a short stretch of sequence complementarity located in the apical and internal loops of the interacting domains is sufficient to stabilize the resulting complex.…”

Section: Discussionmentioning

confidence: 99%

“…In all cases, the presence of a short stretch of sequence complementarity located in the apical and internal loops of the interacting domains is sufficient to stabilize the resulting complex. A peculiarity shown by all these systems is that the G-C rich stems flank the internal interacting loop (Aldaz-Carroll et al 2002;Brunel et al 2002;Da Rocha Gomes et al 2004). Interestingly, this feature is also shown by 5BSL3.2, further supporting the ALIL interaction model.…”

Section: Discussionmentioning

confidence: 99%

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A long-range RNA–RNA interaction between the 5′ and 3′ ends of the HCV genome

Romero-López¹,

Berzal‐Herranz²

2009

RNA

112

146

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The RNA genome of the hepatitis C virus (HCV) contains multiple conserved structural cis domains that direct protein synthesis, replication, and infectivity. The untranslatable regions (UTRs) play essential roles in the HCV cycle. Uncapped viral RNAs are translated via an internal ribosome entry site (IRES) located at the 59 UTR, which acts as a scaffold for recruiting multiple protein factors. Replication of the viral genome is initiated at the 39 UTR. Bioinformatics methods have identified other structural RNA elements thought to be involved in the HCV cycle. The 5BSL3.2 motif, which is embedded in a cruciform structure at the 39 end of the NS5B coding sequence, contributes to the three-dimensional folding of the entire 39 end of the genome. It is essential in the initiation of replication. This paper reports the identification of a novel, strand-specific, long-range RNA-RNA interaction between the 59 and 39 ends of the genome, which involves 5BSL3.2 and IRES motifs. Mutants harboring substitutions in the apical loop of domain IIId or in the internal loop of 5BSL3.2 disrupt the complex, indicating these regions are essential in initiating the kissing interaction. No complex was formed when the UTRs of the related foot and mouth disease virus were used in binding assays, suggesting this interaction is specific for HCV sequences. The present data firmly suggest the existence of a higher-order structure that may mediate a protein-independent circularization of the HCV genome. The 59-39 end bridge may have a role in viral translation modulation and in the switch from protein synthesis to RNA replication.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A long-range RNA–RNA interaction between the 5′ and 3′ ends of the HCV genome

Romero-López¹,

Berzal‐Herranz²

2009

RNA

112

146

View full text Add to dashboard Cite

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“…IIa/IIa-14t and SL1/5-39 complexes IIa-14t and 5-39 are two aptamers selected from SELEX (systematic evolution of ligands by exponential enrichment) (Da Rocha Gomes et al 2004). The two aptamers tightly bind to the IIa domain and SL1 domain of HCV, respectively.…”

Section: Comparison Of Our Model With Other Existing Modelsmentioning

confidence: 99%

“…The two aptamers tightly bind to the IIa domain and SL1 domain of HCV, respectively. The 2D structures of IIa/IIa-14t (Da Rocha Gomes et al 2004) and SL1/5-39 complexes (Aldaz-Carroll et al 2002) were determined from biochemical experiments. We predicted the structures using the two-step procedure described in the Theory and Model.…”

Section: Comparison Of Our Model With Other Existing Modelsmentioning

confidence: 99%

Predicting structure and stability for RNA complexes with intermolecular loop–loop base-pairing

Cao

Chen

2014

RNA

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RNA loop-loop interactions are essential for genomic RNA dimerization and regulation of gene expression. In this article, a statistical mechanics-based computational method that predicts the structures and thermodynamic stabilities of RNA complexes with loop-loop kissing interactions is described. The method accounts for the entropy changes for the formation of loop-loop interactions, which is a notable advancement that other computational models have neglected. Benchmark tests with several experimentally validated systems show that the inclusion of the entropy parameters can indeed improve predictions for RNA complexes. Furthermore, the method can predict not only the native structures of RNA/RNA complexes but also alternative metastable structures. For instance, the model predicts that the SL1 domain of HIV-1 RNA can form two different dimer structures with similar stabilities. The prediction is consistent with experimental observation. In addition, the model predicts two different binding sites for hTR dimerization: One binding site has been experimentally proposed, and the other structure, which has a higher stability, is structurally feasible and needs further experimental validation.

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“…Viral load which reflect the ability of HCV to replicate was not affected by these mutations. However, the importance of stem-loop II for IRES function has been discussed controversially and the changes that occurred in the base-paired regions have not been demonstrated as affecting the translational activity of HCV-IRES (Da Rocha Gomes et al, 2004;Honda et al, 1999a;Kalliampakou et al, 2002;Odreman-Macchioli et al, 2001;Reynolds et al, 1996;Rijnbrand et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

IRES complexity before IFN‐alpha treatment and evolution of the viral load at the early stage of treatment in peripheral blood mononuclear cells from chronic hepatitis C patients

Thélu

Leroy

Ramzan

et al. 2007

Journal of Medical Virology

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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Determinants of apical loop–internal loop RNA–RNA interactions involving the HCV IRES

Cited by 35 publications

References 28 publications

A long-range RNA–RNA interaction between the 5′ and 3′ ends of the HCV genome

A long-range RNA–RNA interaction between the 5′ and 3′ ends of the HCV genome

Predicting structure and stability for RNA complexes with intermolecular loop–loop base-pairing

IRES complexity before IFN‐alpha treatment and evolution of the viral load at the early stage of treatment in peripheral blood mononuclear cells from chronic hepatitis C patients

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