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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.