RESUMO
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.
Assuntos
Hepacivirus/genética , Sítios Internos de Entrada Ribossomal/genética , MicroRNAs/genética , Iniciação Traducional da Cadeia Peptídica , Códon/genética , Regulação da Expressão Gênica , Hepatite C/genética , Hepatite C/virologia , Humanos , MicroRNAs/biossíntese , Proteína I de Ligação a Poli(A)/genética , Biossíntese de Proteínas/genética , RNA Viral/biossíntese , RNA Viral/genética , Subunidades Ribossômicas Menores de Eucariotos/genéticaAssuntos
MicroRNAs/fisiologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Regulação Viral da Expressão Gênica , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , RNA Viral/genética , RNA Viral/metabolismo , Células Tumorais Cultivadas , Replicação Viral/genéticaAssuntos
Publicações Seriadas , Estudantes , França/epidemiologia , Humanos , Fator de Impacto de Revistas , Conhecimento , Laboratórios/estatística & dados numéricos , Idioma , Percepção , Publicações Seriadas/normas , Publicações Seriadas/estatística & dados numéricos , Publicações Seriadas/tendências , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Universidades/estatística & dados numéricosRESUMO
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.
