Skip to Main content Skip to Navigation
Journal articles

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

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.
Complete list of metadatas

Cited literature [46 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02433705
Contributor : Myriam Bodescot <>
Submitted on : Thursday, January 9, 2020 - 1:44:58 PM
Last modification on : Friday, January 10, 2020 - 1:19:16 AM

File

journal.pbio.3000532.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Violeta Heras, Susana Sangiao-Alvarellos, Maria Manfredi-Lozano, María Sanchez-Tapia, Francisco Ruiz-Pino, et al.. Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3. PLoS Biology, Public Library of Science, 2019, 17 (11), pp.e3000532. ⟨10.1371/journal.pbio.3000532⟩. ⟨inserm-02433705⟩

Share

Metrics

Record views

123

Files downloads

67