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Cell. 2014 Aug 14;158(4):764-777. doi: 10.1016/j.cell.2014.06.023.

Stem-loop recognition by DDX17 facilitates miRNA processing and antiviral defense.

Author information

1
Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
2
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
4
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.

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.

PMID:
25126784
PMCID:
PMC4134512
DOI:
10.1016/j.cell.2014.06.023
[Indexed for MEDLINE]
Free PMC Article

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