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Mammarenaviruses are enveloped viruses with a bisegmented negativestranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic mRNAs bearing a capped 5' untranslated region (UTR) and lacking 3' poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open reading frame and transcripts bearing modified 5' and/or 3' UTR were evaluated in a cellbased translation assay. We found that the presence of the cap structure at the 5' end dramatically increases translation efficiency and that the viral 5' UTR comprises stimulatory signals while the 3' UTR,specifically the presence of a terminal C+G-rich sequence and/or a stem-loop structure, down-modulates translation. Additionally, translation was profoundly reduced in eukaryotic initiation factor (eIF) 4G-inactivated cells, whereas depletion of intracellular levels of eIF4E had less impact on virus-like mRNA translation than on a cell-like transcript. Translation efficiency was independent of NP expression or TCRV infection. Our results indicate that TCRV mRNAs are translated using a cap-dependent mechanism, whose efficiency relies on the interplay between stimulatory signals in the 5' UTR and a negative modulatory element in the 3' UTR. The low dependence on eIF4E suggests that viral mRNAs may engage yet-unknown noncanonical host factors for a cap-dependent initiation mechanism. © 2017 American Society for Microbiology.


Documento: Artículo
Título:Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
Autor:Foscaldi, S.; D'Antuono, A.; Noval, M.G.; Gay, G.P.; Scolaro, L.; Lopez, N.
Filiación:Centro de Virología Animal, Instituto de Ciencia y Tecnología Dr. Cesar Milstein, Consejo Nacional de Ciencia y Tecnología, Buenos Aires, Argentina
Fundación Instituto Leloir, Buenos Aires, Argentina
Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Department of Microbiology, New York University, Alexandria Center for Life Sciences, New York, NY, United States
Palabras clave:Arenavirus; MRNA; Translation; initiation factor 4E; initiation factor 4G; messenger RNA; nucleocapsid protein; viral protein; 3' untranslated region; 5' untranslated region; initiation factor 4E; initiation factor 4G; messenger RNA; regulatory RNA sequence; 3' untranslated region; 5' untranslated region; Article; carboxy terminal sequence; controlled study; down regulation; gene sequence; gene structure; genetic transcription; nonhuman; priority journal; protein blood level; protein expression; reporter gene; RNA interference; RNA sequence; RNA translation; Tacaribe virus; translation regulation; virus gene; 3' untranslated region; 5' untranslated region; animal; cell line; gene expression regulation; genetics; host pathogen interaction; human; metabolism; New World arenavirus; protein synthesis; regulatory RNA sequence; 3' Untranslated Regions; 5' Untranslated Regions; Animals; Arenaviruses, New World; Cell Line; Eukaryotic Initiation Factor-4E; Eukaryotic Initiation Factor-4G; Gene Expression Regulation, Viral; Host-Pathogen Interactions; Humans; Protein Biosynthesis; Regulatory Sequences, Ribonucleic Acid; RNA, Messenger
Título revista:Journal of Virology
Título revista abreviado:J. Virol.
CAS:3' Untranslated Regions; 5' Untranslated Regions; Eukaryotic Initiation Factor-4E; Eukaryotic Initiation Factor-4G; Regulatory Sequences, Ribonucleic Acid; RNA, Messenger


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---------- APA ----------
Foscaldi, S., D'Antuono, A., Noval, M.G., Gay, G.P., Scolaro, L. & Lopez, N. (2017) . Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors. Journal of Virology, 91(14).
---------- CHICAGO ----------
Foscaldi, S., D'Antuono, A., Noval, M.G., Gay, G.P., Scolaro, L., Lopez, N. "Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors" . Journal of Virology 91, no. 14 (2017).
---------- MLA ----------
Foscaldi, S., D'Antuono, A., Noval, M.G., Gay, G.P., Scolaro, L., Lopez, N. "Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors" . Journal of Virology, vol. 91, no. 14, 2017.
---------- VANCOUVER ----------
Foscaldi, S., D'Antuono, A., Noval, M.G., Gay, G.P., Scolaro, L., Lopez, N. Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors. J. Virol. 2017;91(14).