title: piRNA-directed cleavage of meiotic transcripts regulates spermatogenesis.
abstract: MIWI catalytic activity is required for spermatogenesis, indicating that piRNA-guided cleavage is critical for germ cell development. To identify meiotic piRNA targets, we augmented the mouse piRNA repertoire by introducing a human meiotic piRNA cluster. This triggered a spermatogenesis defect by inappropriately targeting the piRNA machinery to mouse mRNAs essential for germ cell development. Analysis of such de novo targets revealed a signature for pachytene piRNA target recognition. This enabled identification of both transposable elements and meiotically expressed protein-coding genes as targets of native piRNAs. Cleavage of genic targets began at the pachytene stage and resulted in progressive repression through meiosis, driven at least in part via the ping-pong cycle. Our data support the idea that meiotic piRNA populations must be strongly selected to enable successful spermatogenesis, both driving the response away from essential genes and directing the pathway toward mRNA targets that are regulated by small RNAs in meiotic cells.
authors.affiliation: Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA; Watson School of Biological Sciences, Cold Spring Harbor, New York 11724, USA;
authors.forename: Wee Siong Sho
authors.initials: WS
authors.lastname: Goh
authors.affiliation: Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA; Watson School of Biological Sciences, Cold Spring Harbor, New York 11724, USA; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK;
authors.forename: Ilaria
authors.initials: I
authors.lastname: Falciatori
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor, New York 11724, USA;
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Tam
authors.affiliation: Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA; Watson School of Biological Sciences, Cold Spring Harbor, New York 11724, USA;
authors.forename: Ralph
authors.initials: R
authors.lastname: Burgess
authors.affiliation: Institute of Biomedicine, Department of Physiology, University of Turku, Turku FI-20520, Finland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Meikar
authors.affiliation: Institute of Biomedicine, Department of Physiology, University of Turku, Turku FI-20520, Finland.
authors.forename: Noora
authors.initials: N
authors.lastname: Kotaja
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor, New York 11724, USA;
authors.forename: Molly
authors.initials: M
authors.lastname: Hammell
authors.affiliation: Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA; Watson School of Biological Sciences, Cold Spring Harbor, New York 11724, USA; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK; greg.hannon@cruk.cam.ac.uk.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
mesh_terms: D000818:Animals; D004251:DNA Transposable Elements / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D008540:Meiosis; D051379:Mice; D016366:Open Reading Frames / Q000235:genetics; D049471:Pachytene Stage / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D034741:RNA, Small Interfering
keywords: MIWI; RNA cleavage; exogenous piRNAs; pachytene piRNAs; ping-pong cycle; spermatogenesis defect