Nature 442, 203-207 (13 July 2006) | doi:10.1038/nature04916; Received 18 February 2006; Accepted 17 May 2006; Published online 4 June 2006

A novel class of small RNAs bind to MILI protein in mouse testes

Alexei Aravin1,10,9, Dimos Gaidatzis2,10, Sébastien Pfeffer1,9, Mariana Lagos-Quintana1, Pablo Landgraf1, Nicola Iovino1, Patricia Morris3, Michael J. Brownstein4, Satomi Kuramochi-Miyagawa5, Toru Nakano5, Minchen Chien6, James J. Russo6, Jingyue Ju6,7, Robert Sheridan8, Chris Sander8, Mihaela Zavolan2 and Thomas Tuschl1

Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes1, 2, 3, 4. A subgroup of the Argonaute proteins—known as the 'Piwi family'5—is required for germ- and stem-cell development in invertebrates6, 7, and two Piwi members—MILI and MIWI—are essential for spermatogenesis in mouse8, 9. Here we describe a new class of small RNAs that bind to MILI in mouse male germ cells, where they accumulate at the onset of meiosis. The sequences of the over 1,000 identified unique molecules share a strong preference for a 5' uridine, but otherwise cannot be readily classified into sequence families. Genomic mapping of these small RNAs reveals a limited number of clusters, suggesting that these RNAs are processed from long primary transcripts. The small RNAs are 26–31 nucleotides (nt) in length—clearly distinct from the 21–23 nt of microRNAs (miRNAs) or short interfering RNAs (siRNAs)—and we refer to them as 'Piwi-interacting RNAs' or piRNAs. Orthologous human chromosomal regions also give rise to small RNAs with the characteristics of piRNAs, but the cloned sequences are distinct. The identification of this new class of small RNAs provides an important starting point to determine the molecular function of Piwi proteins in mammalian spermatogenesis.

  1. Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, Box 186, New York, New York 10021, USA
  2. Biozentrum, Universität Basel, Klingelbergstr 50-70, CH-4056 Basel, Switzerland
  3. Population Council, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
  4. J. Craig Venter Institute, Functional Genomics, 9704 Medical Center Drive, Rockville, Maryland 20850, USA
  5. Department of Pathology, Medical School, Graduate School of Frontier Biosciences, Osaka University, Yamada-oka 2-2 Suita, Osaka 565-0871, Japan
  6. Columbia Genome Center, Russ Berrie Pavilion, 1150 St. Nicholas Avenue, New York, New York 10032, USA
  7. Department of Chemical Engineering, Columbia University, 500 West 120 Street, New York, New York 10027, USA
  8. Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
  9. †Present addresses: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA (A.A.); CNRS-UPR 2357, IBMP, 12 rue du Général Zimmer, 67084 Strasbourg Cedex, France (S.P.)
  10. *These authors contributed equally to this work

Correspondence to: Mihaela Zavolan2Thomas Tuschl1 Correspondence and requests for materials should be addressed to M.Z. (Email: Mihaela.Zavolan@unibas.ch) or T.T. (Email: ttuschl@rockefeller.edu). Sequences of the piRNAs determined in this paper are given in Supplementary Tables 4 and 9.


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