title: Adaptive regulation of testis gene expression and control of male fertility by the Drosophila hairpin RNA pathway. [Corrected].
abstract: Although endogenous siRNAs (endo-siRNAs) have been described in many species, still little is known about their endogenous utility. Here, we show that Drosophila hairpin RNAs (hpRNAs) generate an endo-siRNA class with predominant expression in testes. Although hpRNAs are universally recently evolved, we identify highly complementary protein-coding targets for all hpRNAs. Importantly, we find broad evidence for evolutionary divergences that preferentially maintain compensatory pairing between hpRNAs and targets, serving as first evidence for adaptive selection for siRNA-mediated target regulation in metazoans. We demonstrate organismal impact of hpRNA activity, since knockout of hpRNA1 derepresses its target ATP synthase-β in testes and compromises spermatogenesis and male fertility. Moreover, we reveal surprising male-specific impact of RNAi factors on germ cell development and fertility, consistent with testis-directed function of the hpRNA pathway. Finally, the collected hpRNA loci chronicle an evolutionary timeline that reflects their origins from prospective target genes, mirroring a strategy described for plant miRNAs.
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10065, USA.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Wen
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10065, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Duan
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10065, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bejarano
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10065, USA.
authors.forename: Katsutomo
authors.initials: K
authors.lastname: Okamura
authors.affiliation: Cell Biology Program, The Hospital for Sick Children, PGCRL, 686 Bay Street, Room 15.9716, Toronto, ON M5G 0A4, Canada.
authors.forename: Lacramioara
authors.initials: L
authors.lastname: Fabian
authors.affiliation: Cell Biology Program, The Hospital for Sick Children, PGCRL, 686 Bay Street, Room 15.9716, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Brill
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10065, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Bortolamiol-Becet
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10065, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Martin
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: J Graham
authors.initials: JG
authors.lastname: Ruby
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10065, USA. Electronic address: laie@mskcc.org.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005298:Fertility / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000254:growth & development / Q000378:metabolism; D013737:Testis / Q000254:growth & development / Q000378:metabolism*
chemical_list: D019476:Insect Proteins; D021122:Protein Subunits; D034741:RNA, Small Interfering; D025261:Mitochondrial Proton-Translocating ATPases