Unknown

Dataset Information

0

The antiviral protein viperin regulates chondrogenic differentiation via CXCL10 protein secretion.


ABSTRACT: Viperin (also known as radical SAM domain-containing 2 (RSAD2)) is an interferon-inducible and evolutionary conserved protein that participates in the cell's innate immune response against a number of viruses. Viperin mRNA is a substrate for endoribonucleolytic cleavage by RNase mitochondrial RNA processing (MRP) and mutations in the RNase MRP small nucleolar RNA (snoRNA) subunit of the RNase MRP complex cause cartilage-hair hypoplasia (CHH), a human developmental condition characterized by metaphyseal chondrodysplasia and severe dwarfism. It is unknown how CHH-pathogenic mutations in RNase MRP snoRNA interfere with skeletal development, and aberrant processing of RNase MRP substrate RNAs is thought to be involved. We hypothesized that viperin plays a role in chondrogenic differentiation. Using immunohistochemistry, real-time quantitative PCR, immunoblotting, ELISA, siRNA-mediated gene silencing, plasmid-mediated gene overexpression, label-free MS proteomics, and promoter reporter bioluminescence assays, we discovered here that viperin is expressed in differentiating chondrocytic cells and regulates their protein secretion and the outcome of chondrogenic differentiation by influencing transforming growth factor ? (TGF-?)/SMAD family 2/3 (SMAD2/3) activity via C-X-C motif chemokine ligand 10 (CXCL10). Of note, we observed disturbances in this viperin-CXCL10-TGF-?/SMAD2/3 axis in CHH chondrocytic cells. Our results indicate that the antiviral protein viperin controls chondrogenic differentiation by influencing secretion of soluble proteins and identify a molecular route that may explain impaired chondrogenic differentiation of cells from individuals with CHH.

SUBMITTER: Steinbusch MMF 

PROVIDER: S-EPMC6442052 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

The antiviral protein viperin regulates chondrogenic differentiation via CXCL10 protein secretion.

Steinbusch Mandy M F MMF   Caron Marjolein M J MMJ   Surtel Don A M DAM   van den Akker Guus G H GGH   van Dijk Paul J PJ   Friedrich Franziska F   Zabel Bernhard B   van Rhijn Lodewijk W LW   Peffers Mandy J MJ   Welting Tim J M TJM  

The Journal of biological chemistry 20190204 13


Viperin (also known as radical SAM domain-containing 2 (RSAD2)) is an interferon-inducible and evolutionary conserved protein that participates in the cell's innate immune response against a number of viruses. <i>Viperin</i> mRNA is a substrate for endoribonucleolytic cleavage by RNase mitochondrial RNA processing (MRP) and mutations in the RNase MRP small nucleolar RNA (snoRNA) subunit of the RNase MRP complex cause cartilage-hair hypoplasia (CHH), a human developmental condition characterized  ...[more]

Similar Datasets

2019-02-15 | PXD006999 | Pride
| S-EPMC3207276 | biostudies-other
| S-EPMC2778571 | biostudies-literature
| S-EPMC3149979 | biostudies-literature
| S-EPMC5313200 | biostudies-literature
| S-EPMC10548561 | biostudies-literature
| S-EPMC5970183 | biostudies-literature
| S-EPMC64994 | biostudies-literature
| S-EPMC8254119 | biostudies-literature
| S-EPMC3992657 | biostudies-literature