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Nat Commun. 2014;5:3259. doi: 10.1038/ncomms4259.

Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus.

Author information

1
1] MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, P.R. China [2].
2
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, P.R. China.
3
Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
4
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, P.R. China.

Abstract

The ribonucleoprotein (RNP) of the influenza A virus is responsible for the transcription and replication of viral RNA in the nucleus. These processes require interplay between host factors and RNP components. Here, we report that the Fragile X mental retardation protein (FMRP) targets influenza virus RNA synthesis machinery and facilitates virus replication both in cell culture and in mice. We demonstrate that FMRP transiently associates with viral RNP and stimulates viral RNP assembly through RNA-mediated interaction with the nucleoprotein. Furthermore, the KH2 domain of FMRP mediates its association with the nucleoprotein. A point mutation (I304N) in the KH2 domain, identified from a Fragile X syndrome patient, disrupts the FMRP-nucleoprotein association and abolishes the ability of FMRP to participate in viral RNP assembly. We conclude that FMRP is a critical host factor used by influenza viruses to facilitate viral RNP assembly. Our observation reveals a mechanism of influenza virus RNA synthesis and provides insights into FMRP functions.

PMID:
24514761
DOI:
10.1038/ncomms4259
[Indexed for MEDLINE]

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