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

Ryan H. Moy, Brian S. Cole, Ari Yasunaga, Beth Gold, Ganesh Shankarling, Andrew Varble, Jerome M. Molleston, Benjamin R. Tenoever, Kristen W. Lynch, Sara Cherry

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

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.

Original languageEnglish
Pages (from-to)764-777
Number of pages14
JournalCell
Volume158
Issue number4
DOIs
StatePublished - 14 Aug 2014

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