RT Journal Article
T1 Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3.
A1 Heras, Violeta
A1 Sangiao-Alvarellos, Susana
A1 Manfredi-Lozano, Maria
A1 Sanchez-Tapia, María J
A1 Ruiz-Pino, Francisco
A1 Roa, Juan
A1 Lara-Chica, Maribel
A1 Morrugares-Carmona, Rosario
A1 Jouy, Nathalie
A1 Abreu, Ana P
A1 Prevot, Vincent
A1 Belsham, Denise
A1 Vazquez, Maria J
A1 Calzado, Marco A
A1 Pinilla, Leonor
A1 Gaytan, Francisco
A1 Latronico, Ana C
A1 Kaiser, Ursula B
A1 Castellano, Juan M
A1 Tena-Sempere, Manuel
K1 Rats
K1 Sequence analysis, DNA
K1 Sexual maturation
K1 Ubiquitin-protein ligases
AB 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.
PB Public Library of Science
YR 2019
FD 2019-10-25
LK http://hdl.handle.net/10668/14651
UL http://hdl.handle.net/10668/14651
LA en
NO Heras V, Sangiao-Alvarellos S, Manfredi-Lozano M, Sanchez-Tapia MJ, Ruiz-Pino F, Roa J, et al. Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3. PLoS Biol. 2019 Nov 7;17(11):e3000532
DS RISalud
RD Apr 5, 2025