title: Conserved piRNA Expression from a Distinct Set of piRNA Cluster Loci in Eutherian Mammals.
abstract: The Piwi pathway is deeply conserved amongst animals because one of its essential functions is to repress transposons. However, many Piwi-interacting RNAs (piRNAs) do not base-pair to transposons and remain mysterious in their targeting function. The sheer number of piRNA cluster (piC) loci in animal genomes and infrequent piRNA sequence conservation also present challenges in determining which piC loci are most important for development. To address this question, we determined the piRNA expression patterns of piC loci across a wide phylogenetic spectrum of animals, and reveal that most genic and intergenic piC loci evolve rapidly in their capacity to generate piRNAs, regardless of known transposon silencing function. Surprisingly, we also uncovered a distinct set of piC loci with piRNA expression conserved deeply in Eutherian mammals. We name these loci Eutherian-Conserved piRNA cluster (ECpiC) loci. Supporting the hypothesis that conservation of piRNA expression across ~100 million years of Eutherian evolution implies function, we determined that one ECpiC locus generates abundant piRNAs antisense to the STOX1 transcript, a gene clinically associated with preeclampsia. Furthermore, we confirmed reduced piRNAs in existing mouse mutations at ECpiC-Asb1 and -Cbl, which also display spermatogenic defects. The Asb1 mutant testes with strongly reduced Asb1 piRNAs also exhibit up-regulated gene expression profiles. These data indicate ECpiC loci may be specially adapted to support Eutherian reproduction.
authors.affiliation: Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, United States of America.
authors.forename: Gung-Wei
authors.initials: GW
authors.lastname: Chirn
authors.affiliation: Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, United States of America.
authors.forename: Reazur
authors.initials: R
authors.lastname: Rahman
authors.affiliation: Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, United States of America.
authors.forename: Yuliya A
authors.initials: YA
authors.lastname: Sytnikova
authors.affiliation: Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, United States of America.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Matts
authors.affiliation: Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, United States of America.
authors.forename: Mei
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gerlach
authors.affiliation: Mathematics Department and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Yu
authors.affiliation: Mathematics Department and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Berger
authors.affiliation: Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Naramura
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kile
authors.affiliation: Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, United States of America.
authors.forename: Nelson C
authors.initials: NC
authors.lastname: Lau
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D008322:Mammals / Q000145:classification / Q000235:genetics*; D005810:Multigene Family; D034741:RNA, Small Interfering / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering