Polypyrimidine-Tract-Binding Protein Isoforms Differentially Regulate the Hepatitis C Virus Internal Ribosome Entry Site

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dc.contributor.authorAngulo, Jenniffer
dc.contributor.authorCaceres, C. Joaquin
dc.contributor.authorContreras, Nataly
dc.contributor.authorFernandez-Garcia, Leandro
dc.contributor.authorChamond, Nathalie
dc.contributor.authorAmeur, Melissa
dc.contributor.authorSargueil, Bruno
dc.contributor.authorLopez-Lastra, Marcelo
dc.date.accessioned2025-01-20T20:18:05Z
dc.date.available2025-01-20T20:18:05Z
dc.date.issued2023
dc.description.abstractTranslation initiation of the hepatitis C virus (HCV) mRNA depends on an internal ribosome entry site (IRES) that encompasses most of the 5 ' UTR and includes nucleotides of the core coding region. This study shows that the polypyrimidine-tract-binding protein (PTB), an RNA-binding protein with four RNA recognition motifs (RRMs), binds to the HCV 5 ' UTR, stimulating its IRES activity. There are three isoforms of PTB: PTB1, PTB2, and PTB4. Our results show that PTB1 and PTB4, but not PTB2, stimulate HCV IRES activity in HuH-7 and HEK293T cells. In HuH-7 cells, PTB1 promotes HCV IRES-mediated initiation more strongly than PTB4. Mutations in PTB1, PTB4, RRM1/RRM2, or RRM3/RRM4, which disrupt the RRM's ability to bind RNA, abrogated the protein's capacity to stimulate HCV IRES activity in HuH-7 cells. In HEK293T cells, PTB1 and PTB4 stimulate HCV IRES activity to similar levels. In HEK293T cells, mutations in RRM1/RRM2 did not impact PTB1 ' s ability to promote HCV IRES activity; and mutations in PTB1 RRM3/RRM4 domains reduced, but did not abolish, the protein's capacity to stimulate HCV IRES activity. In HEK293T cells, mutations in PTB4 RRM1/RRM2 abrogated the protein's ability to promote HCV IRES activity, and mutations in RRM3/RRM4 have no impact on PTB4 ability to enhance HCV IRES activity. Therefore, PTB1 and PTB4 differentially stimulate the IRES activity in a cell type-specific manner. We conclude that PTB1 and PTB4, but not PTB2, act as IRES transacting factors of the HCV IRES.
dc.fuente.origenWOS
dc.identifier.doi10.3390/v15010008
dc.identifier.eissn1999-4915
dc.identifier.urihttps://doi.org/10.3390/v15010008
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92440
dc.identifier.wosidWOS:000927749500001
dc.issue.numero1
dc.language.isoen
dc.revistaViruses-basel
dc.rightsacceso restringido
dc.subjectHCV
dc.subjectIRES
dc.subjectPTB
dc.subjectITAF
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePolypyrimidine-Tract-Binding Protein Isoforms Differentially Regulate the Hepatitis C Virus Internal Ribosome Entry Site
dc.typeartículo
dc.volumen15
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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