title: A trans-homologue interaction between reciprocally imprinted miR-127 and Rtl1 regulates placenta development.
abstract: The paternally expressed imprinted retrotransposon-like 1 (Rtl1) is a retrotransposon-derived gene that has evolved a function in eutherian placentation. Seven miRNAs, including miR-127, are processed from a maternally expressed antisense Rtl1 transcript (Rtl1as) and regulate Rtl1 levels through RNAi-mediated post-transcriptional degradation. To determine the relative functional role of Rtl1as miRNAs in Rtl1 dosage, we generated a mouse specifically deleted for miR-127. The miR-127 knockout mice exhibit placentomegaly with specific defects within the labyrinthine zone involved in maternal-fetal nutrient transfer. Although fetal weight is unaltered, specific Rtl1 transcripts and protein levels are increased in both the fetus and placenta. Phenotypic analysis of single (ΔmiR-127/Rtl1 or miR-127/ΔRtl1) and double (ΔmiR-127/ΔRtl1) heterozygous miR-127- and Rtl1-deficient mice indicate that Rtl1 is the main target gene of miR-127 in placental development. Our results demonstrate that miR-127 is an essential regulator of Rtl1, mediated by a trans-homologue interaction between reciprocally imprinted genes on the maternally and paternally inherited chromosomes.
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Ito
authors.affiliation: Centre for Trophoblast Research, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Sferruzzi-Perri
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Edwards
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Bjorn T
authors.initials: BT
authors.lastname: Adalsteinsson
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Allen
authors.affiliation: Laboratory of Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648.
authors.forename: Tsui-Han
authors.initials: TH
authors.lastname: Loo
authors.affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Moe
authors.initials: M
authors.lastname: Kitazawa
authors.affiliation: School of Health Sciences, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kaneko-Ishino
authors.affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Ishino
authors.affiliation: Laboratory of Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Stewart
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK Centre for Trophoblast Research, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK afsmith@mole.bio.cam.ac.uk.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
mesh_terms: D000818:Animals; D002875:Chromosomes / Q000378:metabolism / Q000648:ultrastructure; D003433:Crosses, Genetic; D005091:Exons; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D005810:Multigene Family; D010641:Phenotype; D010920:Placenta / Q000378:metabolism / Q000502:physiology*; D010929:Placentation / Q000235:genetics; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D035683:MicroRNAs; C533109:Mirn127 microRNA, mouse; D011257:Pregnancy Proteins; C526773:Rtl1 protein, mouse
keywords: Genomic imprinting; Mir127; Placenta development; Rtl1 (Peg11); miR-127