Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.

Viruses that generate capped RNA lacking 2'O methylation on the first ribose are severely affected by the antiviral activity of Type I interferons. We used proteome-wide affinity purification coupled to mass spectrometry to identify human and mouse proteins specifically binding to capped RNA wi...

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Autores principales:	Matthias Habjan, Philipp Hubel, Livia Lacerda, Christian Benda, Cathleen Holze, Christian H Eberl, Angelika Mann, Eveline Kindler, Cristina Gil-Cruz, John Ziebuhr, Volker Thiel, Andreas Pichlmair
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/84761bfef68c48ab8b7cff68a5fa0d6c
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spelling	oai:doaj.org-article:84761bfef68c48ab8b7cff68a5fa0d6c2021-11-18T06:07:34ZSequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.1553-73661553-737410.1371/journal.ppat.1003663https://doaj.org/article/84761bfef68c48ab8b7cff68a5fa0d6c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098121/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Viruses that generate capped RNA lacking 2'O methylation on the first ribose are severely affected by the antiviral activity of Type I interferons. We used proteome-wide affinity purification coupled to mass spectrometry to identify human and mouse proteins specifically binding to capped RNA with different methylation states. This analysis, complemented with functional validation experiments, revealed that IFIT1 is the sole interferon-induced protein displaying higher affinity for unmethylated than for methylated capped RNA. IFIT1 tethers a species-specific protein complex consisting of other IFITs to RNA. Pulsed stable isotope labelling with amino acids in cell culture coupled to mass spectrometry as well as in vitro competition assays indicate that IFIT1 sequesters 2'O-unmethylated capped RNA and thereby impairs binding of eukaryotic translation initiation factors to 2'O-unmethylated RNA template, which results in inhibition of translation. The specificity of IFIT1 for 2'O-unmethylated RNA serves as potent antiviral mechanism against viruses lacking 2'O-methyltransferase activity and at the same time allows unperturbed progression of the antiviral program in infected cells.Matthias HabjanPhilipp HubelLivia LacerdaChristian BendaCathleen HolzeChristian H EberlAngelika MannEveline KindlerCristina Gil-CruzJohn ZiebuhrVolker ThielAndreas PichlmairPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 10, p e1003663 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Matthias Habjan Philipp Hubel Livia Lacerda Christian Benda Cathleen Holze Christian H Eberl Angelika Mann Eveline Kindler Cristina Gil-Cruz John Ziebuhr Volker Thiel Andreas Pichlmair Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.
description	Viruses that generate capped RNA lacking 2'O methylation on the first ribose are severely affected by the antiviral activity of Type I interferons. We used proteome-wide affinity purification coupled to mass spectrometry to identify human and mouse proteins specifically binding to capped RNA with different methylation states. This analysis, complemented with functional validation experiments, revealed that IFIT1 is the sole interferon-induced protein displaying higher affinity for unmethylated than for methylated capped RNA. IFIT1 tethers a species-specific protein complex consisting of other IFITs to RNA. Pulsed stable isotope labelling with amino acids in cell culture coupled to mass spectrometry as well as in vitro competition assays indicate that IFIT1 sequesters 2'O-unmethylated capped RNA and thereby impairs binding of eukaryotic translation initiation factors to 2'O-unmethylated RNA template, which results in inhibition of translation. The specificity of IFIT1 for 2'O-unmethylated RNA serves as potent antiviral mechanism against viruses lacking 2'O-methyltransferase activity and at the same time allows unperturbed progression of the antiviral program in infected cells.
format	article
author	Matthias Habjan Philipp Hubel Livia Lacerda Christian Benda Cathleen Holze Christian H Eberl Angelika Mann Eveline Kindler Cristina Gil-Cruz John Ziebuhr Volker Thiel Andreas Pichlmair
author_facet	Matthias Habjan Philipp Hubel Livia Lacerda Christian Benda Cathleen Holze Christian H Eberl Angelika Mann Eveline Kindler Cristina Gil-Cruz John Ziebuhr Volker Thiel Andreas Pichlmair
author_sort	Matthias Habjan
title	Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.
title_short	Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.
title_full	Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.
title_fullStr	Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.
title_full_unstemmed	Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.
title_sort	sequestration by ifit1 impairs translation of 2'o-unmethylated capped rna.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/84761bfef68c48ab8b7cff68a5fa0d6c
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Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.

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