MKRN3 Interacts With Several Proteins Implicated in Puberty Timing but Does Not Influence GNRH1 Expression

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Yellapragada , V , Liu , X , Lund , C , Känsäkoski , J , Pulli , K , Vuoristo , S , Lundin , K , Tuuri , T , Varjosalo , M & Raivio , T 2019 , ' MKRN3 Interacts With Several Proteins Implicated in Puberty Timing but Does Not Influence GNRH1 Expression ' , Frontiers in Endocrinology , vol. 10 , 48 . https://doi.org/10.3389/fendo.2019.00048

Title: MKRN3 Interacts With Several Proteins Implicated in Puberty Timing but Does Not Influence GNRH1 Expression
Author: Yellapragada, Venkatram; Liu, Xiaonan; Lund, Carina; Känsäkoski, Johanna; Pulli, Kristiina; Vuoristo, Sanna; Lundin, Karolina; Tuuri, Timo; Varjosalo, Markku; Raivio, Taneli
Contributor organization: STEMM - Stem Cells and Metabolism Research Program
Department of Physiology
Faculty of Medicine
University of Helsinki
Medicum
Institute of Biotechnology
Helsinki Institute of Life Science HiLIFE
Raivio Group
Department of Obstetrics and Gynecology
Clinicum
Timo Pyry Juhani Otonkoski / Principal Investigator
Molecular Systems Biology
Children's Hospital
HUS Gynecology and Obstetrics
HUS Children and Adolescents
Date: 2019-02-08
Language: eng
Number of pages: 10
Belongs to series: Frontiers in Endocrinology
ISSN: 1664-2392
DOI: https://doi.org/10.3389/fendo.2019.00048
URI: http://hdl.handle.net/10138/300020
Abstract: Paternally-inherited loss-of-function mutations in makorin ring finger protein 3 gene (MKRN3) underlie central precocious puberty. To investigate the puberty-related mechanism(s) of MKRN3 in humans, we generated two distinct bi-allelic MKRN3 knock-out human pluripotent stem cell lines, Del 1 and Del 2, and differentiated them into GNRH1-expressing neurons. Both Del 1 and Del 2 clones could be differentiated into neuronal progenitors and GNRH1-expressing neurons, however, the relative expression of GNRH1 did not differ from wild type cells (P = NS). Subsequently, we investigated stable and dynamic protein-protein interaction (PPI) partners of MKRN3 by stably expressing it in HEK cells followed by mass spectrometry analyses. We found 81 high-confidence novel protein interaction partners, which are implicated in cellular processes such as insulin signaling, RNA metabolism and cell-cell adhesion. Of the identified interactors, 20 have been previously implicated in puberty timing. In conclusion, our stem cell model for generation of GNRH1 -expressing neurons did not offer mechanistic insight for the role of MKRN3 in puberty initiation. The PPI data, however, indicate that MKRN3 may regulate puberty by interacting with other puberty-related proteins. Further studies are required to elucidate the possible mechanisms and outcomes of these interactions.
Subject: MKRN3
puberty timing
protein interaction
GNRH1
CRISPR/Cas9
CENTRAL PRECOCIOUS PUBERTY
GENOME-WIDE ASSOCIATION
IMPRINTED GENE
HYPOGONADOTROPIC HYPOGONADISM
LEVELS DECLINE
MUTATIONS
AGE
LOCI
METAANALYSIS
DIAGNOSIS
3111 Biomedicine
1184 Genetics, developmental biology, physiology
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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