Dataset Information

A regulatory loop between miR-132 and miR-125b involved in gonadotrope cells desensitization to GnRH.

ABSTRACT: The GnRH neurohormone is the main activator of the pituitary gonadotropins, LH and FSH. Here we investigated the contribution of microRNAs in mediating GnRH activation. We first established that miR-125b targets several actors of G?q/11 signalling pathway, without altering G?s pathway. We then showed that a G?s-mediated, PKA-dependent phosphorylation of NSun2 methyltransferase leads to miR-125b methylation and thereby induces its down-regulation. We demonstrated that NSun2 mRNA is a target of miR-132 and that NSun2 may be inactivated by the PP1? phosphatase. Time-course analysis of GnRH treatment revealed an initial NSun2-dependent down-regulation of miR-125b with consecutive up-regulation of LH and FSH expression. Increase of miR-132 and of the catalytic subunit of PP1? then contributed to NSun2 inactivation and to the return of miR-125b to its steady-state level. The G?q/11-dependent pathway was thus again silenced, provoking the down-regulation of LH, FSH and miR-132. Overall, this study reveals that a regulatory loop that tends to maintain or restore high and low levels of miR-125b and miR-132, respectively, is responsible for gonadotrope cells desensitization to sustained GnRH. A dysregulation of this loop might be responsible for the inverted dynamics of these two miRNAs reported in several neuronal and non-neuronal pathologies.

SUBMITTER: Lannes J

PROVIDER: S-EPMC4990909 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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A regulatory loop between miR-132 and miR-125b involved in gonadotrope cells desensitization to GnRH.

Lannes Jérôme J L'hôte David D Fernandez-Vega Ambra A Garrel Ghislaine G Laverrière Jean-Noël JN Cohen-Tannoudji Joëlle J Quérat Bruno B

Scientific reports 20160819

The GnRH neurohormone is the main activator of the pituitary gonadotropins, LH and FSH. Here we investigated the contribution of microRNAs in mediating GnRH activation. We first established that miR-125b targets several actors of Gαq/11 signalling pathway, without altering Gαs pathway. We then showed that a Gαs-mediated, PKA-dependent phosphorylation of NSun2 methyltransferase leads to miR-125b methylation and thereby induces its down-regulation. We demonstrated that NSun2 mRNA is a target of mi ...[more]

PMID: 27539363

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Dataset Information

A regulatory loop between miR-132 and miR-125b involved in gonadotrope cells desensitization to GnRH.

Publications

A regulatory loop between miR-132 and miR-125b involved in gonadotrope cells desensitization to GnRH.

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