title: Stem-loop recognition by DDX17 facilitates miRNA processing and antiviral defense.
abstract: DEAD-box helicases play essential roles in RNA metabolism across species, but emerging data suggest that they have additional functions in immunity. Through RNAi screening, we identify an evolutionarily conserved and interferon-independent role for the DEAD-box helicase DDX17 in restricting Rift Valley fever virus (RVFV), a mosquito-transmitted virus in the bunyavirus family that causes severe morbidity and mortality in humans and livestock. Loss of Drosophila DDX17 (Rm62) in cells and flies enhanced RVFV infection. Similarly, depletion of DDX17 but not the related helicase DDX5 increased RVFV replication in human cells. Using crosslinking immunoprecipitation high-throughput sequencing (CLIP-seq), we show that DDX17 binds the stem loops of host pri-miRNA to facilitate their processing and also an essential stem loop in bunyaviral RNA to restrict infection. Thus, DDX17 has dual roles in the recognition of stem loops: in the nucleus for endogenous microRNA (miRNA) biogenesis and in the cytoplasm for surveillance against structured non-self-elements.
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ryan H
authors.initials: RH
authors.lastname: Moy
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Cole
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: Yasunaga
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Gold
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Shankarling
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Varble
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Molleston
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: tenOever
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kristen W
authors.initials: KW
authors.lastname: Lynch
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: cherrys@mail.med.upenn.edu.
authors.forename: Sara
authors.initials: S
authors.lastname: Cherry
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000276:immunology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000276:immunology / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D055029:Inverted Repeat Sequences; D035683:MicroRNAs / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry; D012296:Rift Valley fever virus / Q000502:physiology*; D014779:Virus Replication
chemical_list: D029721:Drosophila Proteins; D035683:MicroRNAs; D012367:RNA, Viral; C102004:DDX17 protein, human; D053487:DEAD-box RNA Helicases; C000593028:Rm62 protein, Drosophila