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
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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