Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3
Autor: | Juan Carlos Roa, Ursula B. Kaiser, Leonor Pinilla, Susana Sangiao-Alvarellos, Ana Claudia Latronico, Maria Manfredi-Lozano, Violeta Heras, Francisco Gaytan, Vincent Prevot, Juan M. Castellano, Ana Paula Abreu, Denise D. Belsham, Manuel Tena-Sempere, Maribel Lara-Chica, Marco A. Calzado, Rosario Morrugares-Carmona, María J. Sanchez-Tapia, María Jesús Vázquez, Francisco Ruiz-Pino, Nathalie Jouy |
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Přispěvatelé: | Department of Cell Biology, Physiology and Immunology [Cordoue, Espagne], University of Córdoba [Córdoba]-Instituto Maimonides de Investigación Biomédica de Córdoba [Cordoue, Espagne] (IMIBIC)-Hospital Universitario Reina Sofia [Cordoue, Espagne], Department of Medicine [La Corogne, Espagne], Faculty of Health Sciences [La Corogne, Espagne], University of A Coruña (UDC)-University of A Coruña (UDC), Instituto de Investigación Biomédica de A Coruña [La Corogne, Espagne] (INIBIC), A Coruña University Hospital [La Corogne, Espagne], Laboratory of Development and Plasticity of the Neuroendocrine Brain [Lille], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Division of Endocrinology, Diabetes and Hypertension [Boston, États-Unis], Harvard Medical School [Boston] (HMS)-Brigham and Women's Hospital [Boston], Department of Physiology [Toronto, ON, Canada], Medical Sciences Building [Toronto, ON, Canada], University of Toronto-University of Toronto, CIBER Fisiopatología de la Obesidad y Nutrición [Cordoue, Espagne] (CIBEROBN), Instituto de Salud Carlos III [Madrid] (ISC), Unidade de Endocrinologia do Desenvolvimento [São Paulo, Brésil], Faculdade de Medicina da Universidade de São Paulo [São Paulo, Brésil], FiDiPro Program [Turku, Finlande], Institute of Biomedicine [Turku, Finlande], University of Turku-University of Turku, This work was supported by grants BFU2014-57581-P and BFU2017-83934-P (Ministerio de Economıa y Competitividad, Spain, co-funded with EU funds from FEDER Program), project PIE-00005 (Flexi-Met, Instituto de Salud Carlos III, Ministerio de Sanidad, Spain), Project P12-FQM-01943 (Junta de Andalucıa, Spain), and Project REP-655232 (ReprObesity, European Union). CIBER Fisiopatologıa de la Obesidad y Nutricion is an initiative of Instituto de Salud Carlos III., European Project: 655232,H2020,H2020-MSCA-IF-2014,ReprObesity(2016), Bodescot, Myriam, Overweight-induced Hypogonadism as major factor for the generation and/or perpetuation of Metabolic Co-morbidities of Obesity: Contribution of Epigenetic Regulatory Mechanisms - ReprObesity - - H20202016-10-01 - 2018-09-30 - 655232 - VALID, Universidad de Córdoba = University of Córdoba [Córdoba]-Instituto Maimonides de Investigación Biomédica de Córdoba [Cordoue, Espagne] (IMIBIC)-Hospital Universitario Reina Sofia [Cordoue, Espagne], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Manfredi-Lozano, Maria [0000-0003-3801-1955], Lara-Chica, Maribel [0000-0003-2908-9929], Prevot, Vincent [0000-0001-7185-3615], Belsham, Denise [0000-0002-7065-8591], Calzado, Marco A [0000-0002-5338-535X], Castellano, Juan M [0000-0003-3981-6683], Tena-Sempere, Manuel [0000-0002-4741-5567], Apollo - University of Cambridge Repository |
Rok vydání: | 2019 |
Předmět: |
Untranslated region
Male Physiology Artificial Gene Amplification and Extension Biochemistry Polymerase Chain Reaction 0302 clinical medicine Endocrinology Untranslated Regions Animal Cells Medicine and Health Sciences Sexual Maturation Biology (General) Regulation of gene expression [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Neurons 0303 health sciences General Neuroscience Messenger RNA Gene Expression Regulation Developmental Brain [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Nucleic acids Female Cellular Types Anatomy General Agricultural and Biological Sciences Puberty onset Research Article medicine.medical_specialty 3' Utr medicine.drug_class QH301-705.5 Yellow Fluorescent Protein Period (gene) Ubiquitin-Protein Ligases Hypothalamus Repressor 030209 endocrinology & metabolism Biology Research and Analysis Methods General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Internal medicine microRNA medicine Genetics Animals Non-coding RNA Molecular Biology Techniques Psychological repression Molecular Biology 030304 developmental biology Natural antisense transcripts Binding Sites General Immunology and Microbiology Endocrine Physiology Puberty Biology and Life Sciences Proteins Sequence Analysis DNA Cell Biology Reverse Transcriptase-Polymerase Chain Reaction Rats Gene regulation MicroRNAs Luminescent Proteins Estrogen Cellular Neuroscience RNA Gene expression Neuroscience |
Zdroj: | PLoS Biology PLoS Biology, Public Library of Science, 2019, 17 (11), pp.e3000532. ⟨10.1371/journal.pbio.3000532⟩ PLoS Biology, 2019, 17 (11), pp.e3000532. ⟨10.1371/journal.pbio.3000532⟩ RUC. Repositorio da Universidade da Coruña instname PLoS Biology, Vol 17, Iss 11, p e3000532 (2019) |
ISSN: | 1545-7885 1544-9173 |
Popis: | Mkrn3, the maternally imprinted gene encoding the makorin RING-finger protein-3, has recently emerged as putative pubertal repressor, as evidenced by central precocity caused by MKRN3 mutations in humans; yet, the molecular underpinnings of this key regulatory action remain largely unexplored. We report herein that the microRNA, miR-30, with three binding sites in a highly conserved region of its 3′ UTR, operates as repressor of Mkrn3 to control pubertal onset. Hypothalamic miR-30b expression increased, while Mkrn3 mRNA and protein content decreased, during rat postnatal maturation. Neonatal estrogen exposure, causing pubertal alterations, enhanced hypothalamic Mkrn3 and suppressed miR-30b expression in female rats. Functional in vitro analyses demonstrated a strong repressive action of miR-30b on Mkrn3 3′ UTR. Moreover, central infusion during the juvenile period of target site blockers, tailored to prevent miR-30 binding to Mkrn3 3′ UTR, reversed the prepubertal down-regulation of hypothalamic Mkrn3 protein and delayed female puberty. Collectively, our data unveil a novel hypothalamic miRNA pathway, involving miR-30, with a prominent role in the control of puberty via Mkrn3 repression. These findings expand our current understanding of the molecular basis of puberty and its disease states. The microRNA miR-30 suppresses the expression of Mkrn3 (a known repressor of puberty) in the hypothalamus by binding to a highly conserved region of its 3’ untranslated region, representing a novel mechanism for finely modulating the tempo of puberty. |
Databáze: | OpenAIRE |
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