title: Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus.
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.
authors: 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].
authors: Zhuo
authors: Z
authors: Zhou
authors: 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].
authors: Mengmeng
authors: M
authors: Cao
authors: 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].
authors: Yang
authors: Y
authors: Guo
authors: 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.
authors: Lili
authors: L
authors: Zhao
authors: 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.
authors: Jingfeng
authors: J
authors: Wang
authors: 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.
authors: Xue
authors: X
authors: Jia
authors: 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.
authors: Jianguo
authors: J
authors: Li
authors: 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.
authors: Conghui
authors: C
authors: Wang
authors: Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors: Gülsah
authors: G
authors: Gabriel
authors: 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.
authors: Qinghua
authors: Q
authors: Xue
authors: Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, P.R. China.
authors: Yonghong
authors: Y
authors: Yi
authors: 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.
authors: Sheng
authors: S
authors: Cui
authors: 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.
authors: Qi
authors: Q
authors: Jin
authors: 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.
authors: Jianwei
authors: J
authors: Wang
authors: 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.
authors: Tao
authors: T
authors: Deng
mesh_terms: D000818:Animals; D004285:Dogs; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D018345:Mice, Knockout; D012367:RNA, Viral / Q000096:biosynthesis*; D012261:Ribonucleoproteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012367:RNA, Viral; D012261:Ribonucleoproteins; D014764:Viral Proteins