Biology Faculty Articles

Title

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

Document Type

Article

Publication Date

3-18-2008

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Keywords

innate immunity, mRNA export, vesicular stomatitis virus

ISSN

1091-6490

Volume

105

Issue/No.

11

First Page

4173

Last Page

4178

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.