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

Frontiers in Endocrinology
Venkatram YellapragadaTaneli Raivio

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-r...Continue Reading

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Citations

Jul 12, 2019·Frontiers in Endocrinology·Sasha R Howard
Jun 27, 2020·Journal of the Endocrine Society·Stephanie A RobertsUrsula B Kaiser
Jul 28, 2020·International Journal of Molecular Sciences·Jessica L BellStefan Hüttelmaier
Aug 29, 2019·Archives of Endocrinology and Metabolism·Ana Pinheiro Machado CantonAna Claudia Latronico
Jul 21, 2020·The Journal of Clinical Investigation·Ali Abbara, Waljit S Dhillo
Jan 1, 2021·The Journal of Clinical Endocrinology and Metabolism·Carlos Eduardo SeraphimAna Claudia Latronico
Nov 21, 2020·Pediatric Research·Tero VarimoTaneli Raivio
Jun 19, 2021·The Journal of Experimental Medicine·Ke LiYuexiang Wang

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Methods Mentioned

BETA
PCR
transfection
Fluorescence
Reverse Transcription RNA
affinity purification
affinity

Software Mentioned

SEQUEST
DAVID
Integrative Genomics Viewer ( IGV )
Cytoscape
ImageJ

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