Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors

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&...

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Detalles Bibliográficos
Autores principales: Foscaldi, S., D'Antuono, A., Noval, M.G., Gay, G.P., Scolaro, L., Lopez, N.
Formato: JOUR
Materias:
Arenavirus
MRNA
Translation
initiation factor 4E
initiation factor 4G
messenger RNA
nucleocapsid protein
viral protein
3' untranslated region
5' untranslated region
regulatory RNA sequence
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
animal
cell line
gene expression regulation
genetics
host pathogen interaction
human
metabolism
New World arenavirus
protein synthesis
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
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_0022538X_v91_n14_p_Foscaldi
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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.

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