Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation

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dc.contributor.authorInes Barria, Maria
dc.contributor.authorGonzalez, Angel
dc.contributor.authorVera Otarola, Jorge
dc.contributor.authorLeon, Ursula
dc.contributor.authorVollrath, Valeska
dc.contributor.authorMarsac, Delphine
dc.contributor.authorMonasterio, Octavio
dc.contributor.authorPerez Acle, Tomas
dc.contributor.authorSoza, Alejandro
dc.contributor.authorLopez Lastra, Marcelo
dc.date.accessioned2024-01-10T12:04:11Z
dc.date.available2024-01-10T12:04:11Z
dc.date.issued2009
dc.description.abstractThe HCV internal ribosome entry site (IRES) spans a region of similar to 340 nt that encompasses most of the 5' untranslated region (5'UTR) of the viral mRNA and the first 24-40 nt of the core-coding region. To investigate the implication of altering the primary sequence of the 5'UTR on IRES activity, naturally occurring variants of the 5'UTR were isolated from clinical samples and analyzed. The impact of the identified mutations on translation was evaluated in the context of RLuc/FLuc bicistronic RNAs. Results show that depending on their location within the RNA structure, these naturally occurring mutations cause a range of effects on IRES activity. However, mutations within subdomain IIId hinder HCV IRES-mediated translation. In an attempt to explain these data, the dynamic behavior of the subdomain IIId was analyzed by means of molecular dynamics (MD) simulations. Despite the loss of function, MD simulations predicted that mutant G266A/G268U possesses a structure similar to the wt-RNA. This prediction was validated by analyzing the secondary structure of the isolated IIId RNAs by circular dichroism spectroscopy in the presence or absence of Mg2+ ions. These data strongly suggest that the primary sequence of subdomain IIId plays a key role in HCV IRES-mediated translation.
dc.fechaingreso.objetodigital2024-04-26
dc.format.extent15 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1093/nar/gkn1022
dc.identifier.eissn1362-4962
dc.identifier.issn0305-1048
dc.identifier.pubmedidMEDLINE:19106142
dc.identifier.urihttps://doi.org/10.1093/nar/gkn1022
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/75719
dc.identifier.wosidWOS:000263831400038
dc.information.autorucCiencias Biológicas;Barría MI;S/I;12076
dc.information.autorucCiencias Biológicas;González A;S/I;1002683
dc.information.autorucMedicina;León U;S/I;1005748
dc.information.autorucMedicina;López-Lastra M;S/I;84823
dc.information.autorucMedicina;Marsac D;S/I;146335
dc.information.autorucCiencias Biológicas;Pérez-Acle T;S/I;90704
dc.information.autorucMedicina;Soza A;S/I;461
dc.information.autorucMedicina;Vollrath V;S/I;2185
dc.issue.numero3
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final971
dc.pagina.inicio957
dc.publisherOXFORD UNIV PRESS
dc.revistaNUCLEIC ACIDS RESEARCH
dc.rightsacceso abierto
dc.subject5' UNTRANSLATED REGION
dc.subjectMUTATIONAL ANALYSIS
dc.subjectDOMAIN-II
dc.subjectMOLECULAR-DYNAMICS
dc.subjectRNA STRUCTURE
dc.subject80S RIBOSOME
dc.subjectIN-VIVO
dc.subjectINITIATION
dc.subjectIRES
dc.subjectEFFICIENCY
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleAnalysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation
dc.typeartículo
dc.volumen37
sipa.codpersvinculados12076
sipa.codpersvinculados1002683
sipa.codpersvinculados1005748
sipa.codpersvinculados84823
sipa.codpersvinculados146335
sipa.codpersvinculados90704
sipa.codpersvinculados461
sipa.codpersvinculados2185
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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