Publication: Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3.
Loading...
Identifiers
Date
2019-10-25
Authors
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
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
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.
Description
MeSH Terms
Animals
Binding sites
Cell line
Female
Gene expression regulation, developmental
Hypothalamus
Male
MicroRNAs
Binding sites
Cell line
Female
Gene expression regulation, developmental
Hypothalamus
Male
MicroRNAs
DeCS Terms
Hipotálamo
Línea celular
MicroARNs
Regulación del desarrollo de la expresión génica
Sitios de unión
Línea celular
MicroARNs
Regulación del desarrollo de la expresión génica
Sitios de unión
CIE Terms
Keywords
Rats, Sequence analysis, DNA, Sexual maturation, Ubiquitin-protein ligases
Citation
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