Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3
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Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3Autor(es)
Data
2019-11-07Cita bibliográfica
Heras V, Sangiao-Alvarellos S, Manfredi-Lozano M, Sanchez-Tapia MJ, Ruiz-Pino F, Roa J, Lara-Chica M, Morrugares-Carmona R, Jouy N, Abreu AP, Prevot V, Belsham D, Vazquez MJ, Calzado MA, Pinilla L, Gaytan F, Latronico AC, Kaiser UB, Castellano JM, Tena-Sempere M. Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3. PLoS Biol. 2019 Nov 7;17(11):e3000532.
Resumo
[Abstract]
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 30 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 30 UTR. Moreover, central infusion during the juvenile period of
target site blockers, tailored to prevent miR-30 binding to Mkrn3 30 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.
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Creative Commons Attribution 4.0 International License (CC-BY 4.0)
ISSN
15457885