A Third Way to Silence RNA

Two well-characterized RNA silencing pathways use small RNAs. Small interfering RNAs (siRNAs) act as targeting molecules in RNA interference (RNAi), and microRNAs (miRNAs) are encoded in the genome as tiny noncoding RNA genes. Although distinct, these pathways share a number of components, such as the endonuclease Dicer, which produces RNAs with a characteristic length of ~22 nucleotides (nt). Vagin et al. and Lau et al. report the initial characterization of a third putative RNA silencing pathway in animals, characterized by ~30-nt small RNAs in the germline--so-called repeat associated (ra) siRNAs in Drosophila and Piwi-interacting RNAs (piRNAs) in mammals (see the Perspective by Carthew). In both cases, these RNAs map specifically either to the sense or antisense strand, but rarely to both, which suggests that, in contrast to siRNAs and miRNAs, they do not arise from double-stranded precursors. The rasi- and piRNAs purify with Piwi proteins, homologs of the Ago proteins found in RNAi and miRNA pathways. Dicer enzymes do not appear to be involved in the generation of the rasiRNAs and, intriguingly, a weak slicing activity is associated with the piRNA complex. V. V. Vagin, A. Sigova, C. Li, H. Seitz, V. Gvozdev, P. D. Zamore, A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313 , 320-324 (2006). [Abstract] [Full Text] N. C. Lau, A. G. Seto, J. Kim, S. Kuramochi-Miyagawa, T. Nakano, D. P. Bartel, R. E. Kingston, Characterization of the piRNA complex from rat testes. Science 313 , 363-367 (2006). [Abstract] [Full Text] R. W. Carthew, A new RNA dimension to genome control. Science 313 , 305-306 (2006). [Summary] [Full Text]