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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Autores principales:	Noval, María Gabriela, Scolaro, Luis Alberto
Publicado:	2017
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:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0022538X_v91_n14_p_Foscaldi 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

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spelling	paper:paper_0022538X_v91_n14_p_Foscaldi2023-06-08T14:51:26Z Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors Noval, María Gabriela Scolaro, Luis Alberto 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 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. Fil:Noval, M.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Scolaro, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0022538X_v91_n14_p_Foscaldi http://hdl.handle.net/20.500.12110/paper_0022538X_v91_n14_p_Foscaldi
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Noval, María Gabriela Scolaro, Luis Alberto Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
topic_facet	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
description	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.
author	Noval, María Gabriela Scolaro, Luis Alberto
author_facet	Noval, María Gabriela Scolaro, Luis Alberto
author_sort	Noval, María Gabriela
title	Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title_short	Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title_full	Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title_fullStr	Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title_full_unstemmed	Regulation of Tacaribe mammarenavirus translation: Positive 5' and negative 3' elements and role of key cellular factors
title_sort	regulation of tacaribe mammarenavirus translation: positive 5' and negative 3' elements and role of key cellular factors
publishDate	2017
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0022538X_v91_n14_p_Foscaldi http://hdl.handle.net/20.500.12110/paper_0022538X_v91_n14_p_Foscaldi
work_keys_str_mv	AT novalmariagabriela regulationoftacaribemammarenavirustranslationpositive5andnegative3elementsandroleofkeycellularfactors AT scolaroluisalberto regulationoftacaribemammarenavirustranslationpositive5andnegative3elementsandroleofkeycellularfactors
_version_	1768544071935066112

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

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