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Letter
Nature 442, 199-202 (13 July 2006) | doi:10.1038/nature04917; Received 18 February 2006; Accepted 18 May 2006; Published online 4 June 2006
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A germline-specific class of small RNAs binds mammalian Piwi proteins
Angélique Girard1,2, Ravi Sachidanandam1, Gregory J. Hannon1 & Michelle A. Carmell1
- Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
- Ecole Nationale Supérieure des Mines de Paris, 60 boulevard Saint-Michel, 75272 Paris, France
Correspondence to: Gregory J. Hannon1 Correspondence and requests for materials should be addressed to G.J.H. (Email: hannon@cshl.edu). The GenBank accession numbers for piR-1, piR-2 and piR-3 are DQ539889, DQ539890 and DQ539891, respectively. Mouse piRNA accession numbers range from DQ539889 to DQ569912; human piRNA accession numbers range from DQ569913 to DQ601958; and rat piRNA accession numbers range from DQ601959 to DQ628526.
Abstract
Small RNAs associate with Argonaute proteins and serve as sequence-specific guides to regulate messenger RNA stability, protein synthesis, chromatin organization and genome structure1, 2, 3. In animals, Argonaute proteins segregate into two subfamilies4. The Argonaute subfamily acts in RNA interference and in microRNA-mediated gene regulation using 21–22-nucleotide RNAs as guides. The Piwi subfamily is involved in germline-specific events such as germline stem cell maintenance and meiosis. However, neither the biochemical function of Piwi proteins nor the nature of their small RNA guides is known. Here we show that MIWI, a murine Piwi protein, binds a previously uncharacterized class of
29–30-nucleotide RNAs that are highly abundant in testes. We have therefore named these Piwi-interacting RNAs (piRNAs). piRNAs show distinctive localization patterns in the genome, being predominantly grouped into 20–90-kilobase clusters, wherein long stretches of small RNAs are derived from only one strand. Similar piRNAs are also found in human and rat, with major clusters occurring in syntenic locations. Although their function must still be resolved, the abundance of piRNAs in germline cells and the male sterility of Miwi mutants suggest a role in gametogenesis.
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