TY - JOUR
T1 - NFAR-1 and -2 modulate translation and are required for efficient host defense
AU - Pfeifer, Ingrid
AU - Elsby, Rachel
AU - Fernandez, Marilyn
AU - Faria, Paula A.
AU - Nussenzveig, Daniel R.
AU - Lossos, Izidor S.
AU - Fontoura, Beatriz M A
AU - Martin, W. David
AU - Barber, Glen N.
PY - 2008/3/18
Y1 - 2008/3/18
N2 - 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.
AB - 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.
KW - Innate immunity
KW - Vesicular stomatitis virus
KW - mRNA export
UR - http://www.scopus.com/inward/record.url?scp=41949112042&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41949112042&partnerID=8YFLogxK
U2 - 10.1073/pnas.0711222105
DO - 10.1073/pnas.0711222105
M3 - Article
C2 - 18337511
AN - SCOPUS:41949112042
SN - 0027-8424
VL - 105
SP - 4173
EP - 4178
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 11
ER -