%0 Journal Article
%T Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3
%A Ana C. Latronico
%A Ana P. Abreu
%A Denise Belsham
%A Francisco Gaytan
%A Francisco Ruiz-Pino
%A Juan M. Castellano
%A Juan Roa
%A Leonor Pinilla
%A Manuel Tena-Sempere
%A Marco A. Calzado
%A Maria J. Vazquez
%A Maria Manfredi-Lozano
%A Maribel Lara-Chica
%A Mar¨ªa J. Sanchez-Tapia
%A Nathalie Jouy
%A Rosario Morrugares-Carmona
%A Susana Sangiao-Alvarellos
%A Ursula B. Kaiser
%A Vincent Prevot
%A Violeta Heras
%J -
%D 2019
%R 10.1371/journal.pbio.3000532
%X 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¡ä 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¡ä UTR. Moreover, central infusion during the juvenile period of target site blockers, tailored to prevent miR-30 binding to Mkrn3 3¡ä 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
%K Puberty
%K MicroRNAs
%K Untranslated regions
%K Neurons
%K Hypothalamus
%K Polymerase chain reaction
%K Yellow fluorescent protein
%K Reverse transcriptase-polymerase chain reaction
%U https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000532