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Inhibition of hepatitis C virus IRES-mediated translation by small RNAs analogous to stemâ??loop structures of the 5â?²-untranslated region

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Pertenece a: PubMed Central (PMC3 - NLM DTD)  

Descripción: Translation of the hepatitis C virus (HCV) RNA is mediated by the interaction of ribosomes and cellular proteins with an internal ribosome entry site (IRES) located within the 5â?²-untranslated region (5â?²-UTR). We have investigated whether small RNA molecules corresponding to the different stemâ??loop (SL) domains of the HCV IRES, when introduced in trans, can bind to the cellular proteins and antagonize their binding to the viral IRES, thereby inhibiting HCV IRES-mediated translation. We have found that a RNA molecule corresponding to SL III could efficiently inhibit HCV IRES-mediated translation in a dose-dependent manner without affecting cap-dependent translation. The SL III RNA was found to bind to most of the cellular proteins which interacted with the HCV 5â?²-UTR. A smaller RNA corresponding to SL e+f of domain III also strongly and selectively inhibited HCV IRES-mediated translation. This RNA molecule interacted with the ribosomal S5 protein and prevented the recruitment of the 40S ribosomal subunit. This study reveals valuable insights into the role of the SL structures of the HCV IRES in mediating ribosome entry. Finally, these results provide a basis for developing anti-HCV therapy using small RNA molecules mimicking the SL structures of the 5â?²-UTR to specifically block viral RNA translation.

Autor(es): Ray, Partho Sarothi -  Das, Saumitra - 

Id.: 17955127

Idioma: English  - 

Versión: 1.0

Estado: Final

Palabras claveArticles - 

Tipo de recurso: Text  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

: Copyright © 2004 Oxford University Press

Requerimientos técnicos:  Browser: Any - 

Fecha de contribución: 16-feb-2008

Contacto:

Localización:


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