Through innate immunity, organisms mount an immediate and nonspecific attack against infectious pathogens using mechanisms that are largely conserved from invertebrates to mammals. In healthy plants and animals, microRNAs (miRNA) influence gene expression by regulating the cleavage of mRNAs. Some innate immune systems also use RNA interference to suppress infection by targeting viral RNA for degradation. Sabin et al. have now identified Ars2 as a key regulator of the small interfering RNA (siRNA) pathway, where it is required for normal miRNA-mediated silencing and the innate immune response to RNA virus infection. Loss of Ars2 increases susceptibility to RNA viruses in cells and in flies. Ars2 interacts directly with key components of the inhibitory RNA processing machinery, Dicer and Drosha/Pasha, to enhance siRNA processing. Although Ars2 is conserved in mammals, it is not well characterized. This work in Drosophila suggests that the Ars2 homologue and RNA interference may also limit replication of RNA viruses in higher organisms.

Sabin LR, Zhou R, Gruber JJ, Lukinova N, Bambina S, Berman A, Lau CK, Thompson CB, Cherry S (2009). Ars2 regulates both miRNA- and siRNA-dependent silencing and suppresses RNA virus infection in Drosophila. Cell 138, 340– 351.
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2009