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Science 312 (5772): 452-454

Copyright © 2006 by the American Association for the Advancement of Science

RNA Interference Directs Innate Immunity Against Viruses in Adult Drosophila

Xiao-Hong Wang,1* Roghiyh Aliyari,2* Wan-Xiang Li,2 Hong-Wei Li,2 Kevin Kim,4 Richard Carthew,4 Peter Atkinson,3 Shou-Wei Ding1,2{dagger}

Abstract: Innate immunity against bacterial and fungal pathogens is mediated by Toll and immune deficiency (Imd) pathways, but little is known about the antiviral response in Drosophila. Here, we demonstrate that an RNA interference pathway protects adult flies from infection by two evolutionarily diverse viruses. Our work also describes a molecular framework for the viral immunity, in which viral double-stranded RNA produced during infection acts as the pathogen trigger whereas Drosophila Dicer-2 and Argonaute-2 act as host sensor and effector, respectively. These findings establish a Drosophila model for studying the innate immunity against viruses in animals.

1 Graduate Program for Microbiology, University of California, Riverside, CA 92521, USA.
2 Department of Plant Pathology and Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA.
3 Department of Entomology, University of California, Riverside, CA 92521, USA.
4 Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.

* These authors contributed equally to this work. Back

{dagger} To whom correspondence should be addressed. E-mail: dingsw{at}

RNA interference (RNAi) silences gene expression through small interfering RNAs (siRNAs) and microRNAs (miRNAs). In Drosophila melanogaster (1), Dicer-2 (Dcr-2) produces siRNAs, whereas Dicer-1 (Dcr-1) recognizes precursors of miRNAs. The small RNAs are assembled with an Argonaute (Ago) protein into related effector complexes, such as RNA-induced silencing complex (RISC), to guide specific RNA silencing (1).

RNA silencing provides an antiviral mechanism in plants and animals (26). Plant viruses have evolved diverse strategies for evading the RNA silencing immunity, and expression of viral suppressors of RNAi (VSRs) is essential for infection and virulence (6). However, it is unknown whether antiviral silencing in plants is controlled by a specific small RNA pathway targeted by plant VSRs. Bacterial and fungal infections of D. melanogaster induce Toll and immune deficiency (Imd) pathways, leading to transcriptional induction of antimicrobial peptide effectors via nuclear factor {kappa}B (NF-{kappa}B)–like signaling processes (7). However, it has been unclear whether either pathway plays a role in Drosophila innate immunity against viruses (8, 9). Our previous work in cell culture has indicated that RNAi might mediate viral immunity in D. melanogaster (3). Here, we investigated whether RNAi indeed provides protection against virus infection in Drosophila embryos and adults.

Flock house virus (FHV) contains an RNA genome (10) divided among two plus-strand molecules, RNAs 1 and 2. RNA2 (R2) encodes the single virion structural protein, whereas RNA1 (R1) encodes protein A, the viral RNA–dependent RNA polymerase (RdRP), and B2, a VSR (3, 4, 11) expressed after RNA1 replication from its own mRNA, RNA3 (fig. S1). In the absence of R2, R1 replicated autonomously, accumulated to high levels, and produced abundant RNA3 in wild-type (WT) D. melanogaster embryos 30 hours after injection with R1 transcripts synthesized in vitro (Fig. 1, lane 2). No FHV RNAs accumulated in WT embryos injected with R1fs transcripts that contain a frameshift mutation in the RdRP open reading frame (ORF) (Fig. 1, lane 1). FHV RNAs were also not readily detected in WT embryos injected with a second mutant of R1, R1{Delta}B2, which does not express the VSR (Fig. 1, lane 3). However, abundant accumulation of R1{Delta}B2 (Fig. 1, lane 9) but not FR1fs (Fig. 1, lane 7) occurred in mutant Drosophila embryos that carried a homozygous null mutation in ago-2 (ago-2414), which is essential for RNAi in Drosophila (1, 12, 13). These data indicated that viral RNA replication in Drosophila embryos triggers an RNAi-mediated virus clearance in an Ago-2–dependent manner and that effective RNAi suppression by B2 is necessary to achieve normal accumulation of FHV RNAs.

Figure 1 Fig. 1.. Antiviral silencing in Drosophila embryos requires Dcr-2 and Ago-2. Northern blot detection of FHV RNA accumulation in wt, dcr-2L811fsX, and ago-2414 embryos microinjected with in vitro synthesized transcripts R1, R1fs, and R1{Delta}B2, as shown in fig. S1. [View Larger Version of this Image (54K GIF file)]

In Drosophila, Ago-2 acts downstream of Dicer-2 (Dcr-2) to recruit siRNAs, the products of Dcr-2 activity, into the siRNA-dependent RISC (siRISC) (1, 14). Thus, a genetic requirement for ago-2 in FHV RNA clearance implicates Dcr-2 in the RNAi antiviral effector mechanism. To test this hypothesis, we injected R1, R1fs, and R1{Delta}B2 transcripts into embryos carrying a homozygous dcr-2 null mutation, dcr-2L811fsX. Northern blot hybridizations showed that, although FHV RNAs remained undetectable in dcr-2L811fsX embryos injected with R1fs (Fig. 1, lane 4), viral RNA accumulation was rescued in the dcr-2L811fsX embryos injected with R1{Delta}B2 transcripts (Fig. 1, lane 6). This result shows that Dcr-2 is required to initiate RNAi-mediated clearance of FHV RNAs in Drosophila embryos.

To investigate whether the RNAi pathway protects Drosophila from virus infection, we injected adult flies of either WT or dcr-2L811fsX genotype with purified FHV virions. The FHV isolate was of low virulence in WT flies, because about 50% of infected flies survived 15 days postinoculation (dpi) (Fig. 2A) despite a detectable virus load (Fig. 2B, lanes 1 to 6). Inoculation with the same dose of FHV resulted in 60% mortality by 6 dpi and 95% by 15 dpi in dcr-2L811fsX flies (Fig. 2A). Mock inoculation with buffer had little effect on either WT or dcr-2L811fsX flies for as long as observations were made. Both Northern and Western blot analyses revealed that the virus accumulated more rapidly and to much greater levels in dcr-2L811fsX than WT flies (Fig. 2, B and C). Thus, dcr-2 mutants exhibit enhanced disease susceptibility to FHV in comparison with WT flies, demonstrating that Dcr-2 is also required to mount an immune response that protects adult Drosophila against FHV infection.

Figure 2 Fig. 2.. The siRNA pathway controls the innate immunity against FHV in adult flies. (A) Survival of wt, dcr-2L811fsX, and r2d2 mutant flies after FHV infection. Data shown represents mean of triplicates, and the error bars indicate standard deviation. (B and C) Detection of viral RNAs by a probe specific for RNAs 1 and 3 and viral coat protein (CP) by a rabbit anti-FHV serum (18) in wt, dcr-2L811fsX, and r2d2 flies injected with FHV. (D) Detection of FHV siRNAs in the infected adult flies as in (C) (d2, dcr-2; r2, r2d2). The membrane was also probed for microRNA-8 (miR-8) and U6 RNA. nt, nucleotides. [View Larger Version of this Image (35K GIF file)]

R2D2 contains tandem double-stranded RNA (dsRNA)–binding domains and forms a heterodimer with Dcr-2 in vivo that is required for siRNA loading into RISC (1, 15). We found that flies homozygous for a loss-of-function mutation in r2d2 exhibited a phenotype of enhanced disease susceptibility to FHV infection similar to that of dcr-2L811fsX (Fig. 2). Thus, R2D2 also participates in the innate immunity pathway that protects adult flies from FHV infection. Notably, although FHV accumulated to extremely high levels in both dcr-2 and r2d2 mutant flies, abundant viral siRNAs were detected only in r2d2 mutant flies, and viral siRNAs were below the level of detection in dcr-2L811fsX flies (Fig. 2D). Thus, FHV infection is detected by Dcr-2, leading to production of FHV siRNAs. However, R2D2 is not required for the production but is essential for the function of viral siRNAs, which is consistent with the genetic requirements for processing the artificially introduced dsRNA (1, 15).

To investigate whether the RNAi pathway in Drosophila is specific against nodaviruses and not other classes of RNA viruses, we assessed the susceptibility of WT, dcr-2L811fsX, and r2d2 mutant flies to cricket paralysis virus (CrPV). CrPV contains a nonsegmented plus-strand RNA genome but belongs to a group of picorna-like viruses (16). CrPV is substantially more virulent than FHV in Drosophila, because injection of CrPV at much lower titers resulted in mortality of 70% of WT flies by 15 dpi (Fig. 3A). We found that CrPV also induced enhanced disease susceptibility in both dcr-2 and r2d2 mutant flies (Fig. 3A). About 60% of the infected mutant flies were dead by 6 dpi, and more than 95% were dead by 15 dpi (Fig. 3A). In addition, Northern blots indicated that the virus accumulated more rapidly and to greater levels in the mutant flies (Fig. 3B). Thus, both dcr-2 and r2d2 are required for protection of Drosophila against CrPV.

Figure 3 Fig. 3.. Mutant dcr-2 and r2d2 flies exhibit enhanced disease susceptibility to CrPV. (A) Survival of wt, dcr-2L811fsX, and r2d2 mutant flies after CrPV infection. Data shown represents mean of triplicates, and the error bars indicate standard deviation. (B) Accumulation of CrPV genomic RNA in WT, dcr-2L811fsX, and r2d2 mutant adults injected with CrPV. [View Larger Version of this Image (37K GIF file)]

CrPV infection of cultured S2 cells induced antiviral silencing, illustrated by detection of CrPV-specific siRNAs (Fig. 4A). Antiviral silencing against FHV in S2 cells induced by FR1gfp as described previously (11) was suppressed by CrPV superinfection, leading to derepression of green fluorescent protein (GFP) (Fig. 4B, left). Two ORFs are encoded by the CrPV RNA genome (16) (fig. S2). We did not observe suppression of antiviral silencing in S2 cells cotransfected with a plasmid expressing either the entire downstream ORF of CrPV or the individual mature virion proteins processed from the polyprotein (Fig. 4C, lanes 4 to 10). In contrast, RNAi suppression was detected after cotransfection with a plasmid expressing either the entire upstream ORF of CrPV or its N-terminal 140 codons (Fig. 4C, pA in lane 1). However, the suppressor activity was not detected after a frameshift mutation was introduced into pA (Fig. 4C, lane 2), thus identifying the N-terminal fragment of 140 amino acids of the CrPV nonstructural polyprotein as a VSR.

Figure 4 Fig. 4.. Induction and suppression of antiviral silencing by CrPV. (A) Accumulation of the genomic RNA and siRNAs of CrPV in infected S2 cells. (B) pFR1gfp directed transcription of a recombinant FHV RNA1 in which the coding sequence for B2 was replaced by that of GFP. S2 cells were transfected with pFR1gfp alone (middle) or pFR1gfp plus either dsRNA-targeting Ago-2 (right) or CrPV superinfection (left). (C) Identification of CrPV RNAi suppressor. Cells were cotransfected with pFR1gfp and a plasmid as indicated on top of each lane (fig. S2), and total RNA was analyzed for the accumulation of pFR1gfp-encoded RNA1 and RNA3. P, the empty plasmid; VP, the virion protein precursor; V1, VP1; V2, VP2; V3, VP3; V4, VP4; V0, VP0 (precursor for VP3 and VP4); A, the first 140 codons of the upstream ORF; {Delta}A, a frameshift mutant of A; and b, the first 107 codons of the upstream ORF. NS1 is an RNAi suppressor of influenza A virus as described previously (11). [View Larger Version of this Image (25K GIF file)]

In D. melanogaster, Imd signaling is stimulated by Gram negative (Gram) bacterial infection, whereas Toll signaling is triggered by Gram positive (Gram+) bacterial infection (7, 17). To determine whether loss of the RNAi pathway initiated by Dcr-2 had an impact on the Toll and Imd signaling processes, we subjected WT, dcr-2L811fsX, and r2d2 mutant flies to immune challenge by inoculation with Escherichia coli (Gram) or Micrococcus luteus (Gram+). Northern blot hybridizations detected substantial transcriptional induction of the antimicrobial peptide gene Diptericin A 6 hours postimmune challenge (hpi) with either E. coli or M. luteus, which declined at 24 hpi (fig. S3) as described (17). Similar induction patterns for Diptericin A were observed in dcr-2L811fsX and r2d2 mutant flies inoculated with Gram+ and Gram bacteria (fig. S3). Furthermore, we found that induction of either Attacin A or Drosomycin by Gram+ and Gram bacteria was also not altered in dcr-2L811fsX and r2d2 mutant flies as compared to WT flies (fig. S3). These results indicate that induction of antimicrobial peptide genes via Toll and Imd signaling pathways is not compromised in dcr-2L811fsX and r2d2 mutant flies.

Nodaviruses and the polio-like CrPV belong to two different superfamilies of animal RNA viruses. We demonstrate that the same set of RNAi pathway genes is required for Drosophila defense against FHV and CrPV and that both viruses encode a potent VSR. These results collectively show that RNAi pathway functions as a common viral immunity mechanism in Drosophila and that RNAi suppression represents a general counterdefensive strategy used by insect viruses. Furthermore, a genetic requirement for Dcr-2, R2D2, and Ago-2 in antiviral silencing establishes a molecular framework for the innate immunity against viruses in D. melanogaster. None of Dcr-2, R2D2, and Ago-2 plays a detectable role in either the production or function of miRNAs in D. melanogaster (1). Thus, our work identifies the dsRNA-siRNA pathway of RNAi as providing the innate immunity against virus infection in Drosophila and establishes that dsRNA produced during virus replication acts as the pathogen trigger whereas Dcr-2 and Ago-2 act as host sensor and effector of the immunity, respectively. These results support and extend the previous findings on antiviral silencing in C. elegans (4, 5).

Although NF-{kappa}B-like signaling in the Toll and Imd pathways do not appear to play a role in the RNAi-directed viral immunity mechanism in D. melanogaster, the fly mutant defective in the Janus kinase (JAK) Hopscotch exhibited a modest increase in susceptibility to infection with Drosophila C virus, suggesting an antiviral role for JAK–signal transducer and activator of transcription (STAT) signaling (8). Nonetheless, we believe that RNAi-based immunity is independent of JAK-STAT signaling, because virus infection is not known to induce the RNAi pathway in Drosophila (8) and FHV induction of the JAK-STAT responsive gene vir-1 was unaltered in the dcr-2 and r2d2 mutants, as shown by our recent work. Because the Toll and Imd pathways are highly conserved in vertebrates (7), the Drosophila model established for RNAi may also be useful for the analyses of the innate antiviral immunity in vertebrates.

References and Notes Back to Top

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Supporting Online Material

Materials and Methods

Figs. S1 to S3


Received for publication 1 February 2006. Accepted for publication 14 March 2006.

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Virus discovery by deep sequencing and assembly of virus-derived small silencing RNAs.
Q. Wu, Y. Luo, R. Lu, N. Lau, E. C. Lai, W.-X. Li, and S.-W. Ding (2010)
PNAS 107, 1606-1611
   Abstract »    Full Text »    PDF »
The endogenous siRNA pathway is involved in heterochromatin formation in Drosophila.
D. Fagegaltier, A.-L. Bouge, B. Berry, E. Poisot, O. Sismeiro, J.-Y. Coppee, L. Theodore, O. Voinnet, and C. Antoniewski (2009)
PNAS 106, 21258-21263
   Abstract »    Full Text »    PDF »
Elevated CO2 suppresses specific Drosophila innate immune responses and resistance to bacterial infection.
I. T. Helenius, T. Krupinski, D. W. Turnbull, Y. Gruenbaum, N. Silverman, E. A. Johnson, P. H. S. Sporn, J. I. Sznajder, and G. J. Beitel (2009)
PNAS 106, 18710-18715
   Abstract »    Full Text »    PDF »
A single Argonaute gene is required for induction of RNA silencing antiviral defense and promotes viral RNA recombination.
Q. Sun, G. H. Choi, and D. L. Nuss (2009)
PNAS 106, 17927-17932
   Abstract »    Full Text »    PDF »
Endo-siRNAs depend on a new isoform of loquacious and target artificially introduced, high-copy sequences.
J. V. Hartig, S. Esslinger, R. Bottcher, K. Saito, and K. Forstemann (2009)
EMBO J. 28, 2932-2944
   Abstract »    Full Text »    PDF »
Low Endocytic pH and Capsid Protein Autocleavage Are Critical Components of Flock House Virus Cell Entry.
A. L. Odegard, M. H. Kwan, H. E. Walukiewicz, M. Banerjee, A. Schneemann, and J. E. Johnson (2009)
J. Virol. 83, 8628-8637
   Abstract »    Full Text »    PDF »
Multiple Dicer Genes in the Early-Diverging Metazoa.
D. de Jong, M. Eitel, W. Jakob, H.-J. Osigus, H. Hadrys, R. DeSalle, and B. Schierwater (2009)
Mol. Biol. Evol. 26, 1333-1340
   Abstract »    Full Text »    PDF »
Dicing of viral replication intermediates during silencing of latent Drosophila viruses.
A. Flynt, N. Liu, R. Martin, and E. C. Lai (2009)
PNAS 106, 5270-5275
   Abstract »    Full Text »    PDF »
The NS3 protein of rice hoja blanca virus complements the RNAi suppressor function of HIV-1 Tat.
E. Schnettler, W. de Vries, H. Hemmes, J. Haasnoot, R. Kormelink, R. Goldbach, and B. Berkhout (2009)
EMBO Rep. 10, 258-263
   Abstract »    Full Text »    PDF »
The evolution of RNAi as a defence against viruses and transposable elements.
D. J Obbard, K. H.J Gordon, A. H Buck, and F. M Jiggins (2009)
Phil Trans R Soc B 364, 99-115
   Abstract »    Full Text »    PDF »
Alphavirus-derived small RNAs modulate pathogenesis in disease vector mosquitoes.
K. M. Myles, M. R. Wiley, E. M. Morazzani, and Z. N. Adelman (2008)
PNAS 105, 19938-19943
   Abstract »    Full Text »    PDF »
Wolbachia and Virus Protection in Insects.
L. M. Hedges, J. C. Brownlie, S. L. O'Neill, and K. N. Johnson (2008)
Science 322, 702
   Abstract »    Full Text »    PDF »
Influenza Virus Protecting RNA: an Effective Prophylactic and Therapeutic Antiviral.
N. J. Dimmock, E. W. Rainsford, P. D. Scott, and A. C. Marriott (2008)
J. Virol. 82, 8570-8578
   Abstract »    Full Text »    PDF »
Virus meets RNAi: Symposium on Antiviral Applications of RNA Interference.
R. P. van Rij (2008)
EMBO Rep. 9, 725-729
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Models of infectious diseases in the fruit fly Drosophila melanogaster.
M. S. Dionne and D. S. Schneider (2008)
Dis. Model. Mech. 1, 43-49
   Abstract »    Full Text »    PDF »
Induction of host defence responses by Drosophila C virus.
L. M. Hedges and K. N. Johnson (2008)
J. Gen. Virol. 89, 1497-1501
   Abstract »    Full Text »    PDF »
Characterization of Hypovirus-Derived Small RNAs Generated in the Chestnut Blight Fungus by an Inducible DCL-2-Dependent Pathway.
X. Zhang, G. C. Segers, Q. Sun, F. Deng, and D. L. Nuss (2008)
J. Virol. 82, 2613-2619
   Abstract »    Full Text »    PDF »
Flock House Virus Induces Apoptosis by Depletion of Drosophila Inhibitor-of-Apoptosis Protein DIAP1.
E. W. Settles and P. D. Friesen (2008)
J. Virol. 82, 1378-1388
   Abstract »    Full Text »    PDF »
Biogenesis and germline functions of piRNAs.
C. Klattenhoff and W. Theurkauf (2008)
Development 135, 3-9
   Abstract »    Full Text »    PDF »
Mouse Cytomegalovirus MicroRNAs Dominate the Cellular Small RNA Profile during Lytic Infection and Show Features of Posttranscriptional Regulation.
L. Dolken, J. Perot, V. Cognat, A. Alioua, M. John, J. Soutschek, Z. Ruzsics, U. Koszinowski, O. Voinnet, and S. Pfeffer (2007)
J. Virol. 81, 13771-13782
   Abstract »    Full Text »    PDF »
The Piwi-piRNA Pathway Provides an Adaptive Defense in the Transposon Arms Race.
A. A. Aravin, G. J. Hannon, and J. Brennecke (2007)
Science 318, 761-764
   Abstract »    Full Text »    PDF »
A Functional Heat Shock Protein 90 Chaperone Is Essential for Efficient Flock House Virus RNA Polymerase Synthesis in Drosophila Cells.
K. M. Castorena, S. A. Weeks, K. A. Stapleford, A. M. Cadwallader, and D. J. Miller (2007)
J. Virol. 81, 8412-8420
   Abstract »    Full Text »    PDF »
Evidence that RNA silencing functions as an antiviral defense mechanism in fungi.
G. C. Segers, X. Zhang, F. Deng, Q. Sun, and D. L. Nuss (2007)
PNAS 104, 12902-12906
   Abstract »    Full Text »    PDF »
Genes misregulated in C. elegans deficient in Dicer, RDE-4, or RDE-1 are enriched for innate immunity genes.
N. C. Welker, J. W. Habig, and B. L. Bass (2007)
RNA 13, 1090-1102
   Abstract »    Full Text »    PDF »
The NS3 protein of Rice hoja blanca tenuivirus suppresses RNA silencing in plant and insect hosts by efficiently binding both siRNAs and miRNAs.
H. Hemmes, L. Lakatos, R. Goldbach, J. Burgyan, and M. Prins (2007)
RNA 13, 1079-1089
   Abstract »    Full Text »    PDF »
Dissection of Double-Stranded RNA Binding Protein B2 from Betanodavirus.
B. J. Fenner, W. Goh, and J. Kwang (2007)
J. Virol. 81, 5449-5459
   Abstract »    Full Text »    PDF »
Suppression of Antiviral Silencing by Cucumber Mosaic Virus 2b Protein in Arabidopsis Is Associated with Drastically Reduced Accumulation of Three Classes of Viral Small Interfering RNAs.
J. A. Diaz-Pendon, F. Li, W.-X. Li, and S.-W. Ding (2007)
PLANT CELL 19, 2053-2063
   Abstract »    Full Text »    PDF »
La Crosse Bunyavirus Nonstructural Protein NSs Serves To Suppress the Type I Interferon System of Mammalian Hosts.
G. Blakqori, S. Delhaye, M. Habjan, C. D. Blair, I. Sanchez-Vargas, K. E. Olson, G. Attarzadeh-Yazdi, R. Fragkoudis, A. Kohl, U. Kalinke, et al. (2007)
J. Virol. 81, 4991-4999
   Abstract »    Full Text »    PDF »
Pervasive Adaptive Evolution among Interactors of the Drosophila Hybrid Inviability Gene, Nup96.
D. C. Presgraves and W. Stephan (2007)
Mol. Biol. Evol. 24, 306-314
   Abstract »    Full Text »    PDF »
RNA silencing of host transcripts by cauliflower mosaic virus requires coordinated action of the four Arabidopsis Dicer-like proteins.
G. Moissiard and O. Voinnet (2006)
PNAS 103, 19593-19598
   Abstract »    Full Text »    PDF »
A pathogen-inducible endogenous siRNA in plant immunity.
S. Katiyar-Agarwal, R. Morgan, D. Dahlbeck, O. Borsani, A. Villegas Jr., J.-K. Zhu, B. J. Staskawicz, and H. Jin (2006)
PNAS 103, 18002-18007
   Abstract »    Full Text »    PDF »
The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster..
R. P. van Rij, M.-C. Saleh, B. Berry, C. Foo, A. Houk, C. Antoniewski, and R. Andino (2006)
Genes & Dev. 20, 2985-2995
   Abstract »    Full Text »    PDF »
A Distinct Small RNA Pathway Silences Selfish Genetic Elements in the Germline.
V. V. Vagin, A. Sigova, C. Li, H. Seitz, V. Gvozdev, and P. D. Zamore (2006)
Science 313, 320-324
   Abstract »    Full Text »    PDF »
Plant science. Viruses face a double defense by plant small RNAs..
P. M. Waterhouse and A. F. Fusaro (2006)
Science 313, 54-55
   Abstract »    Full Text »    PDF »
Hierarchical Action and Inhibition of Plant Dicer-Like Proteins in Antiviral Defense.
A. Deleris, J. Gallego-Bartolome, J. Bao, K. D. Kasschau, J. C. Carrington, and O. Voinnet (2006)
Science 313, 68-71
   Abstract »    Full Text »    PDF »
Innate Immune Defense Through RNA Interference.
J. H. Fritz, S. E. Girardin, and D. J. Philpott (2006)
Sci. STKE 2006, pe27
   Abstract »    Full Text »    PDF »
rasiRNAs, DNA Damage, and Embryonic Axis Specification.
Cold Spring Harb Symp Quant Biol 71, 171-180
   Abstract »    PDF »
Positive and Negative Modulation of Viral and Cellular mRNAs by Liver-specific MicroRNA miR-122.
Cold Spring Harb Symp Quant Biol 71, 369-376
   Abstract »    PDF »

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