RESUMEN
MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by recognizing and hybridizing to a specific sequence generally located in the 3Î untranslated region (UTR) of targeted mRNAs. miRNA-induced inhibition of translation occurs during the initiation step, most probably at the level of ribosome scanning. In this process, the RNA-induced silencing complex interacts both with PABP and the 43S pre-initiation complex to disrupt scanning of the 40S ribosome. However, in some specific cases, miRNAs can stimulate translation. Although the mechanism of miRNA-mediated upregulation is unknown, it appears that the poly(A) tail and the lack of availability of the TNRC6 proteins are amongst major determinants. The genomic RNA of the Hepatitis C Virus is uncapped, non-polyadenylated and harbors a peculiar internal ribosome entry site (IRES) that binds the ribosome directly to the AUG codon. Thus, we have exploited the unique properties of the HCV IRES and other related IRESes (HCV-like) to study how translation initiation can be modulated by miRNAs on these elements. Here, we report that miRNA binding to the 3Î UTR can stimulate translation of a reporter gene given that its expression is driven by an HCV-like IRES and that it lacks a poly(A) tail at its 3Î extremity.
Asunto(s)
Hepacivirus/genética , Sitios Internos de Entrada al Ribosoma/genética , MicroARNs/genética , Iniciación de la Cadena Peptídica Traduccional , Codón/genética , Regulación de la Expresión Génica , Hepatitis C/genética , Hepatitis C/virología , Humanos , MicroARNs/biosíntesis , Proteína I de Unión a Poli(A)/genética , Biosíntesis de Proteínas/genética , ARN Viral/biosíntesis , ARN Viral/genética , Subunidades Ribosómicas Pequeñas de Eucariotas/genéticaAsunto(s)
MicroARNs/fisiología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Progresión de la Enfermedad , Regulación Viral de la Expresión Génica , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , ARN Viral/genética , ARN Viral/metabolismo , Células Tumorales Cultivadas , Replicación Viral/genéticaAsunto(s)
Publicaciones Seriadas , Estudiantes , Francia/epidemiología , Humanos , Factor de Impacto de la Revista , Conocimiento , Laboratorios/estadística & datos numéricos , Lenguaje , Percepción , Publicaciones Seriadas/normas , Publicaciones Seriadas/estadística & datos numéricos , Publicaciones Seriadas/tendencias , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Universidades/estadística & datos numéricosRESUMEN
Translation initiation of the full-length mRNA of the human immunodeficiency virus can occur via several different mechanisms to maintain production of viral structural proteins throughout the replication cycle. HIV-1 viral protein synthesis can occur by the use of both a cap-dependant and IRES-driven mechanism depending on the physiological conditions of the cell and the status of the ongoing infection. For both of these mechanisms there is a need for several viral and cellular co-factors for optimal translation of the viral mRNA. In this review we will describe the mechanism used by the full-length mRNA to initiate translation highlighting the role of co-factors within this process. A particular emphasis will be given to the role of the DDX3 RNA helicase in HIV-1 mRNA translation initiation.