RNA-binding Protein SAMD4 Regulates Skeleton Development Through Translational Inhibition of Mig6 Expression

Overview

Journal Cell Discov

Date 2017 Feb 7

PMID 28163927

Citations 16

Authors

Ningning Niu

Jian-Feng Xiang

Qin Yang

Lijun Wang

Zhanying Wei

Ling-Ling Chen

Li Yang

Weiguo Zou

Affiliations

Soon will be listed here.

Abstract

Protein translation regulation has essential roles in inflammatory responses, cancer initiation and the pathogenesis of several neurodegenerative disorders. However, the role of the regulation of protein translation in mammalian skeleton development has been rarely elaborated. Here we report that the lack of the RNA-binding protein sterile alpha motif domain containing protein 4 (SAMD4) resulted in multiple developmental defects in mice, including delayed bone development and decreased osteogenesis. Samd4-deficient mesenchymal progenitors exhibit impaired osteoblast differentiation and function. Mechanism study demonstrates that SAMD4 binds the Mig6 mRNA and inhibits MIG6 protein synthesis. Consistent with this, Samd4-deficient cells have increased MIG6 protein level and knockdown of Mig6 rescues the impaired osteogenesis in Samd4-deficient cells. Furthermore, Samd4-deficient mice also display chondrocyte defects, which is consistent with the regulation of MIG6 protein level by SAMD4. These findings define SAMD4 as a previously unreported key regulator of osteoblastogenesis and bone development, implying that regulation of protein translation is an important mechanism governing skeletogenesis and that control of protein translation could have therapeutic potential in metabolic bone diseases, such as osteoporosis.

Citing Articles

Dynamic mRNA Stability Buffer Transcriptional Activation During Neuronal Differentiation and Is Regulated by SAMD4A.

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Recent Progress in the Research on RNA-Binding Proteins in Bone Development and Diseases.

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Structural basis for binding of Smaug to the GPCR Smoothened and to the germline inducer Oskar.

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