English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Sequestration by IFIT1 Impairs Translation of 2 ' O-unmethylated Capped RNA

MPS-Authors
/persons/resource/persons78058

Habjan,  Matthias
Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons127956

Hubel,  Philipp
Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons127960

Lacerda,  Livia
Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons77736

Benda,  Christian
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78126

Holze,  Cathleen
Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons77920

Eberl,  Christian H.
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons127958

Mann,  Angelika
Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78510

Pichlmair,  Andreas
Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)

journal.ppat.1003663.pdf
(Any fulltext), 2MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Habjan, M., Hubel, P., Lacerda, L., Benda, C., Holze, C., Eberl, C. H., et al. (2013). Sequestration by IFIT1 Impairs Translation of 2 ' O-unmethylated Capped RNA. PLOS PATHOGENS, 9(10): e1003663. doi:10.1371/journal.ppat.1003663.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0015-81A0-8
Abstract
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 29O-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.