TY - JOUR
T1 - Stem-loop recognition by DDX17 facilitates miRNA processing and antiviral defense
AU - Moy, Ryan H.
AU - Cole, Brian S.
AU - Yasunaga, Ari
AU - Gold, Beth
AU - Shankarling, Ganesh
AU - Varble, Andrew
AU - Molleston, Jerome M.
AU - Tenoever, Benjamin R.
AU - Lynch, Kristen W.
AU - Cherry, Sara
N1 - Funding Information:
We thank A. Spradling for Rm62 mutant flies; A. Bowie for DDX17 siRNA sequences; E. Dardenne for DDX17 plasmid; and M. Tartell for technical help. This work was supported by grants from the National Institutes of Health to S.C. (R01AI074951, U54AI057168, and R01AI095500), K.W.L. (RO1GM103383), and R.H.M. (T32AI007324). S.C. and B.R.T. are recipients of the Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease Award.
PY - 2014/8/14
Y1 - 2014/8/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84908397042&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.06.023
DO - 10.1016/j.cell.2014.06.023
M3 - Article
C2 - 25126784
AN - SCOPUS:84908397042
SN - 0092-8674
VL - 158
SP - 764
EP - 777
JO - Cell
JF - Cell
IS - 4
ER -