Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3
Maribel Lara-Chica; Francisco Ruiz-Pino; Francisco Gaytan; Ursula B. Kaiser; Maria J. Vazquez; Marco A. Calzado; Leonor Pinilla; Rosario Morrugares-Carmona; Manuel Tena-Sempere; Violeta Heras; Ana P. Abreu; Maria Manfredi-Lozano; Juan Roa; Ana C. Latronico; Nathalie Jouy; Susana Sangiao-Alvarellos; Vincent Prevot; María J. Sanchez-Tapia; Denise Belsham; Juan M. Castellano
Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3
Maribel Lara-Chica
Francisco Ruiz-Pino
Francisco Gaytan
Ursula B. Kaiser
Maria J. Vazquez
Marco A. Calzado
Leonor Pinilla
Rosario Morrugares-Carmona
Manuel Tena-Sempere
Violeta Heras
Ana P. Abreu
Maria Manfredi-Lozano
Juan Roa
Ana C. Latronico
Nathalie Jouy
Susana Sangiao-Alvarellos
Vincent Prevot
María J. Sanchez-Tapia
Denise Belsham
Juan M. Castellano
PUBLIC LIBRARY SCIENCE
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042713626
https://urn.fi/URN:NBN:fi-fe2021042713626
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]