%0 Journal Article
%A Heras, Violeta
%A Sangiao-Alvarellos, Susana
%A Manfredi-Lozano, Maria
%A Sanchez-Tapia, María J
%A Ruiz-Pino, Francisco
%A Roa, Juan
%A Lara-Chica, Maribel
%A Morrugares-Carmona, Rosario
%A Jouy, Nathalie
%A Abreu, Ana P
%A Prevot, Vincent
%A Belsham, Denise
%A Vazquez, Maria J
%A Calzado, Marco A
%A Pinilla, Leonor
%A Gaytan, Francisco
%A Latronico, Ana C
%A Kaiser, Ursula B
%A Castellano, Juan M
%A Tena-Sempere, Manuel
%T Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3.
%D 2019
%U http://hdl.handle.net/10668/14651
%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' 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.
%K Rats
%K Sequence analysis, DNA
%K Sexual maturation
%K Ubiquitin-protein ligases
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