Details

Autor(en) / Beteiligte

• Heras, Violeta
• Sangiao-Alvarellos, Susana
• Manfredi-Lozano, Maria
• Sanchez-Tapia, María J
• Ruiz-Pino, Francisco
• Roa, Juan
• Lara-Chica, Maribel
• Morrugares-Carmona, Rosario
• Jouy, Nathalie
• Abreu, Ana P
• Prevot, Vincent
• Belsham, Denise
• Vazquez, Maria J
• Calzado, Marco A
• Pinilla, Leonor
• Gaytan, Francisco
• Latronico, Ana C
• Kaiser, Ursula B
• Castellano, Juan M
• Tena-Sempere, Manuel
• Ong, Ken K.

Titel

Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3

Ist Teil von

• PLoS biology, 2019-11, Vol.17 (11), p.e3000532-e3000532

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2019

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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.