NFAR-1 and -2 modulate translation and are required for efficient host defense

Ingrid Pfeifer, Rachel Elsby, Marilyn Fernandez, Paula A. Faria, Daniel R. Nussenzveig, Izidore Lossos, Beatriz M A Fontoura, W. David Martin, Glen N Barber

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

We report here that the alternatively spliced nuclear factors associated with double-stranded RNA, NFAR-1 (90 kDa) and -2 (110 kDa), are involved in retaining cellular transcripts in intranuclear foci and can regulate the export of mRNA to the cytoplasm. Furthermore, the NFAR proteins were found to remain associated with exported ribonucleoprotein complexes. Loss of NFAR function, which was embryonic-lethal, caused an increase in protein synthesis rates, an effect augmented by the presence of the mRNA export factors TAP, p15, or Rae1. Significantly, NFAR depletion in normal murine fibroblasts rendered these cells dramatically susceptible to vesicular stomatitis virus replication. Collectively, our data demonstrate that the NFARs exert influence on mRNA trafficking and the modulation of translation rates and may constitute an innate immune translational surveillance mechanism important in host defense countermeasures against virus infection.

Original languageEnglish
Pages (from-to)4173-4178
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number11
DOIs
StatePublished - Mar 18 2008

Fingerprint

Messenger RNA
Vesicular Stomatitis
Ribonucleoproteins
Double-Stranded RNA
Virus Diseases
Virus Replication
Cytoplasm
Proteins
Fibroblasts

Keywords

  • Innate immunity
  • mRNA export
  • Vesicular stomatitis virus

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

NFAR-1 and -2 modulate translation and are required for efficient host defense. / Pfeifer, Ingrid; Elsby, Rachel; Fernandez, Marilyn; Faria, Paula A.; Nussenzveig, Daniel R.; Lossos, Izidore; Fontoura, Beatriz M A; Martin, W. David; Barber, Glen N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 11, 18.03.2008, p. 4173-4178.

Research output: Contribution to journalArticle

Pfeifer, Ingrid ; Elsby, Rachel ; Fernandez, Marilyn ; Faria, Paula A. ; Nussenzveig, Daniel R. ; Lossos, Izidore ; Fontoura, Beatriz M A ; Martin, W. David ; Barber, Glen N. / NFAR-1 and -2 modulate translation and are required for efficient host defense. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 11. pp. 4173-4178.
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