NFAR-1 and -2 modulate translation and are required for efficient host defense.
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.
Pfeifer
Ingrid
I
Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Elsby
Rachel
R
Fernandez
Marilyn
M
Faria
Paula A
PA
Nussenzveig
Daniel R
DR
Lossos
Izidor S
IS
Fontoura
Beatriz M A
BM
Martin
W David
WD
Barber
Glen N
GN
D000818:Animals; D002478:Cells, Cultured; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D050779:Nuclear Factor 90 Proteins / Q000235:genetics / Q000378:metabolism*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
C429643:ILF3 protein, human; D050779:Nuclear Factor 90 Proteins; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490522:RAE1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering