A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3
Tekijät: Violeta Heras, Susana Sangiao-Alvarellos, Maria Manfredi-Lozano, María J. Sanchez-Tapia, Francisco Ruiz-Pino, Juan Roa, Maribel Lara-Chica, Rosario Morrugares-Carmona, Nathalie Jouy, Ana P. Abreu, Vincent Prevot, Denise Belsham, Maria J. Vazquez, Marco A. Calzado, Leonor Pinilla, Francisco Gaytan, Ana C. Latronico, Ursula B. Kaiser, Juan M. Castellano, Manuel Tena-Sempere
Kustantaja: PUBLIC LIBRARY SCIENCE
Julkaisuvuosi: 2019
Journal: PLoS Biology
Tietokannassa oleva lehden nimi: PLOS BIOLOGY
Lehden akronyymi: PLOS BIOL
Artikkelin numero: ARTN e3000532
Vuosikerta: 17
Numero: 11
Sivujen määrä: 24
ISSN: 1544-9173
eISSN: 1545-7885
DOI: https://doi.org/10.1371/journal.pbio.3000532
Verkko-osoite: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000532
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/45140280
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
