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PMID: 19632183 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Ars2 regulates both miRNA- and siRNA- dependent silencing and suppresses RNA virus infection in Drosophila.

Cell ·Vol. 138 ·No. 2 ·2009-07-23 ·Pages 340-51

Sabin LR, Zhou R, Gruber JJ, Lukinova N, Bambina S, Berman A, Lau CK, Thompson CB, Cherry S

Abstract

Intrinsic immune responses autonomously inhibit viral replication and spread. One pathway that restricts viral infection in plants and insects is RNA interference (RNAi), which targets and degrades viral RNA to limit infection. To identify additional genes involved in intrinsic antiviral immunity, we screened Drosophila cells for modulators of viral infection using an RNAi library. We identified Ars2 as a key component of Drosophila antiviral immunity. Loss of Ars2 in cells, or in flies, increases susceptibility to RNA viruses. Consistent with its antiviral properties, we found that Ars2 physically interacts with Dcr-2, modulates its activity in vitro, and is required for siRNA-mediated silencing. Furthermore, we show that Ars2 plays an essential role in miRNA-mediated silencing, interacting with the Microprocessor and stabilizing pri-miRNAs. The identification of Ars2 as a player in these small RNA pathways provides new insight into the biogenesis of small RNAs that may be extended to other systems.

MeSH Terms
Animals Drosophila/genetics,immunology,virology Drosophila Proteins/chemistry,genetics,metabolism MicroRNAs/genetics Nuclear Cap-Binding Protein Complex/metabolism RNA Interference RNA, Double-Stranded/metabolism RNA, Small Interfering/genetics Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism Vesiculovirus/genetics,immunology
Chemicals
Ars2 protein, Drosophila Drosophila Proteins MicroRNAs Nuclear Cap-Binding Protein Complex RNA, Double-Stranded RNA, Small Interfering Receptors, TNF-Related Apoptosis-Inducing Ligand
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sabin Leah R
Department of Microbiology, Penn Genome Frontiers Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Zhou Rui
Gruber Joshua J
Lukinova Nina
Bambina Shelly
Berman Allison
Lau Chi-Kong
Thompson Craig B
Cherry Sara
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.04.045
Published
2009-07-23
Pages
340-51
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2717035
Subset
IM
Grants
NIAID NIH HHS · T32 AI007451 · United States
NIGMS NIH HHS · T32 GM-07229 · United States
NIGMS NIH HHS · T32 GM007229 · United States
NIAID NIH HHS · R01AI07451 · United States
NIAID NIH HHS · R01 AI074951-01 · United States
NIAID NIH HHS · R01 AI074951 · United States
Corrections
CommentIn
PMID: 19632172
External Links
PubMed source DOI: 10.1016/j.cell.2009.04.045 PMC Full Text View journal details
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