Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in mice

被引：73

作者：

Hata, Kenji ^{[1
]}

Nishimura, Riko ^{[1
]}

Muramatsu, Shuji ^{[2
]}

Matsuda, Akio ^{[2
]}

Matsubara, Takuma ^{[1
]}

Amano, Katsuhiko ^{[1
]}

Ikeda, Fumiyo ^{[1
]}

Harley, Vincent R. ^{[3
]}

Yoneda, Toshiyuki ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Dent, Dept Mol & Cellular Biochem, Suita, Osaka 5650871, Japan

[2] Asahi KASEI Pharma Corp, Res Ctr, Lab Drug Discovery, Shizuoka, Japan

[3] Monash Med Ctr, Prince Henrys Inst Med Res, Human Mol Genet Lab, Melbourne, Vic, Australia

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2008年 / 118卷 / 09期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

D O I：

10.1172/JCI31373

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The Sox9 transcription factor plays an essential role in promoting chondrogenesis and regulating expression of chondrocyte extracellular-matrix genes. To identify genes that interact with Sox9 in promoting chondrocyte differentiation, we screened a cDNA library generated from the murine chondrogenic ATDC5 cell line to identify activators of the collagen, type II, alpha 1 (Col2al) promoter. Here we have shown that paraspeckle regulatory protein 54-kDa nuclear RNA-binding protein (p54(nrb)) is an essential link between Sox9-regulated transcription and maturation of Sox9-target gene mRNA. We found that p54(nrb) physically interacted with Sox9 and enhanced Sox9-dependent transcriptional activation of the Col2al promoter. In ATDC5 cells, p54(nrb) colocalized with Sox9 protein in nuclear paraspeckle bodies, and knockdown of p54(nrb) suppressed Sox9-dependent Col2al expression and promoter activity. We generated a p54(nrb) mutant construct lacking RNA recognition motifs, and overexpression of mutant p54(nrb) in ATDC5 cells markedly altered the appearance of paraspeckle bodies and inhibited the maturation of Col2al mRNA. The mutant p54nrb inhibited chondrocyte differentiation of mesenchymal cells and mouse metatarsal explants. Furthermore, transgenic mice expressing the mutant p54(nrb) in the chondrocyte lineage exhibited dwarfism associated with impairment of chondrogenesis. These data suggest that p54(nrb) plays.

引用

页码：3098 / 3108

页数：11

共 32 条

[21] Nuclear speckles: A model for nuclear organelles [J].

Lamond, AI ;

Spector, DL .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (08) :605-612

[22] Large-scale identification and characterization of human genes that activate NF-κB and MAPK signaling pathways [J].

Matsuda, A ;

Suzuki, Y ;

Honda, G ;

Muramatsu, S ;

Matsuzaki, O ;

Nagano, Y ;

Doi, T ;

Shimotohno, K ;

Harada, T ;

Nishida, E ;

Hayashi, H ;

Sugano, S .

ONCOGENE, 2003, 22 (21) :3307-3318

[23] Functional and structural studies of wild type SOX9 and mutations causing campomelic dysplasia [J].

McDowall, S ;

Argentaro, A ;

Ranganathan, S ;

Weller, P ;

Mertin, S ;

Mansour, S ;

Tolmie, J ;

Harley, V .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (34) :24023-24030

[24]

METSARANTA M, 1991, J BIOL CHEM, V266, P16862

[25] Functional gene screening system identified TRPV4 as a regulator of chondrogenic differentiation [J].

Muramatsu, Shuji ;

Wakabayashi, Makoto ;

Ohno, Takeshi ;

Amano, Katsuhiko ;

Ooishi, Rika ;

Sugahara, Toshinori ;

Shiojiri, Satoshi ;

Tashiro, Kosuke ;

Suzuki, Yutaka ;

Nishimura, Riko ;

Kuhara, Satoru ;

Sugano, Sumio ;

Yoneda, Toshiyuki ;

Matsuda, Akio .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (44) :32158-32167

[26] Cis-acting intronic elements that regulate cartilage-specific alternative splicing of the type II collagen (Col2) pre-mRNA lie at or near splice site junction sequences flanking exon 2 of the gene [J].

Nishiyama, T ;

Hatano, H ;

Kurosaka, M ;

Bolander, ME ;

Sarkar, G .

JOURNAL OF BONE AND MINERAL RESEARCH, 2003, 18 (09) :1716-1722

[27] AFX1 and p54(nrb): fine mapping, genomic structure, and exclusion as candidate genes of X-linked dystonia parkinsonism [J].

Peters, U ;

Haberhausen, G ;

Kostrzewa, M ;

Nolte, D ;

Muller, U .

HUMAN GENETICS, 1997, 100 (5-6) :569-572

[28] Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation [J].

Preiss, S ;

Argentaro, A ;

Clayton, A ;

John, A ;

Jans, DA ;

Ogata, T ;

Nagai, T ;

Barroso, I ;

Schafer, AJ ;

Harley, VR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (30) :27864-27872

[29]

SAHLAS DJ, 1993, J CELL SCI, V105, P347

[30] Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: Differentiation-dependent gene expression of parathyroid hormone (PTH)/PTH-related peptide receptor [J].

Shukunami, C ;

Shigeno, C ;

Atsumi, T ;

Ishizeki, K ;

Suzuki, F ;

Hiraki, Y .

JOURNAL OF CELL BIOLOGY, 1996, 133 (02) :457-468

← 1 2 3 4 →