title: Nuclear matrix protein Matrin 3 is a regulator of ZAP-mediated retroviral restriction.
abstract: BACKGROUND
  Matrin 3 is a nuclear matrix protein involved in multiple nuclear processes. In HIV-1 infection, Matrin 3 serves as a Rev cofactor important for the cytoplasmic accumulation of HIV-1 transcripts. ZAP is a potent host restriction factor of multiple viruses including retroviruses HIV-1 and MoMuLV. In this study we sought to further characterize Matrin 3 functions in the regulation of HIV gene expression.
  
  
  RESULTS
  Here we describe a function for Matrin 3 as a negative regulator of the ZAP-mediated restriction of retroviruses. Mass spectrometry analysis of Matrin 3-associated proteins uncovered interactions with proteins of the ZAP degradation complex, DDX17 and EXOSC3. Coimmunoprecipitation studies confirmed Matrin 3 associations with DDX17, EXOSC3 and ZAP, in a largely RNA-dependent manner, indicating that RNA is mediating the Matrin 3 interactions with these components of the ZAP degradation complex. Silencing Matrin 3 expression caused a remarkably enhanced ZAP-driven inhibition of HIV-1 and MoMuLV luciferase reporter viruses. This effect was shared with additional nuclear matrix proteins. ZAP targets multiply-spliced HIV-1 transcripts, but in the context of Matrin 3 suppression, this ZAP restriction was broadened to unspliced and multiply-spliced RNAs.
  
  
  CONCLUSIONS
  Here we reveal an unprecedented role for a nuclear matrix protein, Matrin 3, in the regulation of ZAP's antiretroviral activity. Suppressing Matrin 3 powers a heightened and broader ZAP restriction of HIV-1 gene expression. This study suggests that this ZAP regulatory mechanism is shared with additional nuclear matrix proteins.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY, 10032, USA. ae2371@cumc.columbia.edu.
authors.forename: Angela
authors.initials: A
authors.lastname: Erazo
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY, 10032, USA. spg1@cumc.columbia.edu.|Department of Microbiology and Immunology, Columbia University, New York, NY, 10032, USA. spg1@cumc.columbia.edu.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Goff
mesh_terms: D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D016601:RNA-Binding Proteins; C527496:ZC3HAV1 protein, human