Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3.
PLoS Biol
; 17(11): e3000532, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31697675
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 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Maturidade Sexual
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MicroRNAs
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Ubiquitina-Proteína Ligases
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Hipotálamo
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Espanha