Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648

Cell Death & Disease
Zhang MinZhou Yongsheng

Abstract

Histone arginine methylation, which is catalyzed by protein arginine methyltransferases (PRMTs), plays a key regulatory role in various biological processes. Several PRMTs are involved in skeletal development; however, their role in the osteogenic differentiation of mesenchymal stem cells (MSCs) is not completely clear. In this study, we aimed to elucidate the function of PRMT3, a type-I PRMT that catalyzes the formation of ω-mono- or asymmetric dimethyl arginine, in MSCs osteogenesis. We found that PRMT3 promoted MSCs osteogenic commitment and bone remodeling. PRMT3 activated the expression of miR-3648 by enhancing histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) levels at promoter region of the gene. Overexpression of miR-3648 rescued impaired osteogenesis in PRMT3-deficient cells. Moreover, administration of Prmt3 shRNA or a chemical inhibitor of PRMT3 (SGC707) caused an osteopenia phenotype in mice. These results indicate that PRMT3 is a potential therapeutic target for the treatment of bone regeneration and osteopenia disorders.

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Citations

Mar 21, 2021·Nature Reviews. Drug Discovery·Qin WuDalia Barsyte-Lovejoy
May 20, 2021·Experimental & Molecular Medicine·Jee Won HwangYong Kee Kim
Jul 27, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardMohammad Samadian
Aug 25, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardAfshin Taheriazam

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Datasets Mentioned

BETA
GSE124674

Methods Mentioned

BETA
ubiquitination
ChIP-seq
protein assay
PCR
Transfection

Software Mentioned

MACS
SPSS Statistics
ALZET
Burrows Aligner ( BWA

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