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

Kenji Hata, Riko Nishimura, Shuji Muramatsu, Akio Matsuda, Takuma Matsubara, Katsuhiko Amano, Fumiyo Ikeda, Vincent R. Harley, Toshiyuki Yoneda

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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, α 1 (Col2a1) promoter. Here we have shown that paraspeckle regulatory protein 54-kDa nuclear RNA-binding protein (p54nrb) is an essential link between Sox9-regulated transcription and maturation of Sox9-target gene mRNA. We found that p54nrb physically interacted with Sox9 and enhanced Sox9-dependent transcriptional activation of the Col2a1 promoter. In ATDC5 cells, p54nrb colocalized with Sox9 protein in nuclear paraspeckle bodies, and knockdown of p54nrb suppressed Sox9-dependent Col2a1 expression and promoter activity. We generated a p54nrb mutant construct lacking RNA recognition motifs, and overexpression of mutant p54nrb in ATDC5 cells markedly altered the appearance of paraspeckle bodies and inhibited the maturation of Col2a1 mRNA. The mutant p54nrb inhibited chondrocyte differentiation of mesenchymal cells and mouse metatarsal explants. Furthermore, transgenic mice expressing the mutant p54nrb in the chondrocyte lineage exhibited dwarfism associated with impairment of chondrogenesis. These data suggest that p54nrb plays an important role in the regulation of Sox9 function and the formation of paraspeckle bodies during chondrogenesis.

Original languageEnglish
Pages (from-to)3098-3108
Number of pages11
JournalJournal of Clinical Investigation
Volume118
Issue number9
DOIs
Publication statusPublished - Sep 2 2008
Externally publishedYes

Fingerprint

Nuclear RNA
Chondrogenesis
RNA-Binding Proteins
Nuclear Proteins
RNA
Chondrocytes
Proteins
Mutant Proteins
Genes
Dwarfism
Messenger RNA
Metatarsal Bones
Collagen Type I
Gene Library
Transgenic Mice
Transcriptional Activation
Extracellular Matrix
Cell Differentiation
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Hata, K., Nishimura, R., Muramatsu, S., Matsuda, A., Matsubara, T., Amano, K., ... Yoneda, T. (2008). Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in mice. Journal of Clinical Investigation, 118(9), 3098-3108. https://doi.org/10.1172/JCI31373

Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in mice. / Hata, Kenji; Nishimura, Riko; Muramatsu, Shuji; Matsuda, Akio; Matsubara, Takuma; Amano, Katsuhiko; Ikeda, Fumiyo; Harley, Vincent R.; Yoneda, Toshiyuki.

In: Journal of Clinical Investigation, Vol. 118, No. 9, 02.09.2008, p. 3098-3108.

Research output: Contribution to journalArticle

Hata, K, Nishimura, R, Muramatsu, S, Matsuda, A, Matsubara, T, Amano, K, Ikeda, F, Harley, VR & Yoneda, T 2008, 'Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in mice', Journal of Clinical Investigation, vol. 118, no. 9, pp. 3098-3108. https://doi.org/10.1172/JCI31373
Hata, Kenji ; Nishimura, Riko ; Muramatsu, Shuji ; Matsuda, Akio ; Matsubara, Takuma ; Amano, Katsuhiko ; Ikeda, Fumiyo ; Harley, Vincent R. ; Yoneda, Toshiyuki. / Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in mice. In: Journal of Clinical Investigation. 2008 ; Vol. 118, No. 9. pp. 3098-3108.
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