title: Reduced pachytene piRNAs and translation underlie spermiogenic arrest in Maelstrom mutant mice.
abstract: Pachytene piRNAs are a class of Piwi-interacting small RNAs abundant in spermatids of the adult mouse testis. They are processed from piRNA primary transcripts by a poorly understood mechanism and, unlike fetal transposon-derived piRNAs, lack complementary targets in the spermatid transcriptome. We report that immunopurified complexes of a conserved piRNA pathway protein Maelstrom (MAEL) are enriched in MIWI (Piwi partner of pachytene piRNAs), Tudor-domain proteins and processing intermediates of pachytene piRNA primary transcripts. We provide evidence of functional significance of these complexes in Mael129 knockout mice that exhibit spermiogenic arrest with acrosome and flagellum malformation. Mael129-null mutant testes possess low levels of piRNAs derived from MAEL-associated piRNA precursors and exhibit reduced translation of numerous spermiogenic mRNAs including those encoding acrosome and flagellum proteins. These translation defects in haploid round spermatids are likely indirect, as neither MAEL nor piRNA precursors associate with polyribosomes, and they may arise from an imbalance between pachytene piRNAs and MIWI.
authors: Department of Biology, Johns Hopkins University, Baltimore, MD, USA Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA.
authors: Julio
authors: J
authors: Castañeda
authors: Department of Biology, Johns Hopkins University, Baltimore, MD, USA Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA.
authors: Pavol
authors: P
authors: Genzor
authors: Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA.
authors: Godfried W
authors: GW
authors: van der Heijden
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors: Ali
authors: A
authors: Sarkeshik
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors: John R
authors: JR
authors: Yates
authors: Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA ingolia@berkeley.edu bortvin@ciwemb.edu.
authors: Nicholas T
authors: NT
authors: Ingolia
authors: Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA ingolia@berkeley.edu bortvin@ciwemb.edu.
authors: Alex
authors: A
authors: Bortvin
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D049471:Pachytene Stage; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000378:metabolism*; D013087:Spermatids / Q000502:physiology; D013091:Spermatogenesis; D013737:Testis / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C531147:maelstrom protein, mouse
keywords: Piwi; germ cell; maelstrom; mouse; piRNA