title: A novel class of small RNAs bind to MILI protein in mouse testes.
abstract: Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes. A subgroup of the Argonaute proteins--known as the 'Piwi family'--is required for germ- and stem-cell development in invertebrates, and two Piwi members--MILI and MIWI--are essential for spermatogenesis in mouse. 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.
authors.affiliation: Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, Box 186, New York, New York 10021, USA.
authors.forename: Alexei
authors.initials: A
authors.lastname: Aravin
authors.forename: Dimos
authors.initials: D
authors.lastname: Gaidatzis
authors.forename: Sébastien
authors.initials: S
authors.lastname: Pfeffer
authors.forename: Mariana
authors.initials: M
authors.lastname: Lagos-Quintana
authors.forename: Pablo
authors.initials: P
authors.lastname: Landgraf
authors.forename: Nicola
authors.initials: N
authors.lastname: Iovino
authors.forename: Patricia
authors.initials: P
authors.lastname: Morris
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brownstein
authors.forename: Satomi
authors.initials: S
authors.lastname: Kuramochi-Miyagawa
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Minchen
authors.initials: M
authors.lastname: Chien
authors.forename: James J
authors.initials: JJ
authors.lastname: Russo
authors.forename: Jingyue
authors.initials: J
authors.lastname: Ju
authors.forename: Robert
authors.initials: R
authors.lastname: Sheridan
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.forename: Mihaela
authors.initials: M
authors.lastname: Zavolan
authors.forename: Thomas
authors.initials: T
authors.lastname: Tuschl
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D060565:Argonaute Proteins; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000378:metabolism*; D013997:Time Factors
chemical_list: D060565:Argonaute Proteins; C448521:Piwil2 protein, mouse; D011506:Proteins; D012313:RNA