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

doi:10.1172/jci31373

Cited by 77 publications

(90 citation statements)

References 33 publications

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“…HA-tagged Sox9, Sox5, Sox6, Myc-tagged Gli1, Flag-tagged Gli2, and Flagtagged Gli3 expression vectors were used as described previously (Shimoyama et al, 2007;Hata et al, 2008). Myc-tagged dominant-negative Sox9 (aa2-234) and Myc-tagged dominant-negative Gli2 (aa2-968) that lacked the corresponding transcriptional activation domains were also used as described previously (Shimoyama et al, 2007;Hata et al, 2008).…”

Section: Vector Constructionmentioning

confidence: 99%

“…Myc-tagged dominant-negative Sox9 (aa2-234) and Myc-tagged dominant-negative Gli2 (aa2-968) that lacked the corresponding transcriptional activation domains were also used as described previously (Shimoyama et al, 2007;Hata et al, 2008). The human PTHrP gene promoter including the 1120-base pair 5Ј-flanking region (Gallwitz et al, 2002) and the deletion mutants were ligated into the pGL4.10 vector (Promega, Madison, WI).…”

Section: Vector Constructionmentioning

confidence: 99%

“…Recombinant adenoviruses carrying Sox5, Sox6, HA-tagged Sox9, a dominant-negative Myc-tagged Sox9, Ihh, Myc-tagged Gli2, or a dominant-negative Gli2 were constructed by homologous recombination between the expression cosmid cassette (pAxCAwt) and the parental virus genome in 293T cells (Riken Cell Bank) using the adenovirus construction kit (Takara) as described previously (Shimoyama et al, 2007;Hata et al, 2008). Mock adenovirus was used as a control adenovirus.…”

Section: Generation Of Adenovirusesmentioning

confidence: 99%

“…The viruses showed no proliferative activity because of the lack of E1A-E1B. Virus titers were determined using a modified point assay (Shimoyama et al, 2007;Hata et al, 2008).…”

Section: Generation Of Adenovirusesmentioning

confidence: 99%

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Sox9 Family Members Negatively Regulate Maturation and Calcification of Chondrocytes through Up-Regulation of Parathyroid Hormone–related Protein

Amano

Hata²,

Sugita³

et al. 2009

MBoC

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Sox9 is a transcription factor that plays an essential role in chondrogenesis and has been proposed to inhibit the late stages of endochondral ossification. However, the molecular mechanisms underlying the regulation of chondrocyte maturation and calcification by Sox9 remain unknown. In this study, we attempted to clarify roles of Sox9 in the late stages of chondrocyte differentiation. We found that overexpression of Sox9 alone or Sox9 together with Sox5 and Sox6 (Sox5/6/9) inhibited the maturation and calcification of murine primary chondrocytes and up-regulated parathyroid hormone-related protein (PTHrP) expression in primary chondrocytes and the mesenchymal cell line C3H10T1/2. Sox5/6/9 stimulated the early stages of chondrocyte proliferation and development. In contrast, Sox5/6/9 inhibited maturation and calcification of chondrocytes in organ culture. The inhibitory effects of Sox5/6/9 were rescued by treating with anti-PTHrP antibody. Moreover, Sox5/6/9 bound to the promoter region of the PTHrP gene and up-regulated PTHrP gene promoter activity. Interestingly, we also found that the Sox9 family members functionally collaborated with Ihh/Gli2 signaling to regulate PTHrP expression and chondrocyte differentiation. Our results provide novel evidence that Sox9 family members mediate endochondral ossification by up-regulating PTHrP expression in association with Ihh/Gli2 signaling.

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Section: Vector Constructionmentioning

confidence: 99%

Section: Vector Constructionmentioning

confidence: 99%

Section: Generation Of Adenovirusesmentioning

confidence: 99%

“…The viruses showed no proliferative activity because of the lack of E1A-E1B. Virus titers were determined using a modified point assay (Shimoyama et al, 2007;Hata et al, 2008).…”

Section: Generation Of Adenovirusesmentioning

confidence: 99%

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Sox9 Family Members Negatively Regulate Maturation and Calcification of Chondrocytes through Up-Regulation of Parathyroid Hormone–related Protein

Amano

Hata²,

Sugita³

et al. 2009

MBoC

Self Cite

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show abstract

“…52 In addition, p54 nrb interacts specifically with the transcription factor Sox9 and modulates both the promoter activity and alternative splicing of Sox9 targets. 53 Thus, proteins with dual roles in gene-specific transcription and pre-mRNA processing may function in coordinating gene expression. Three domains, i.e.…”

Section: Introductionmentioning

confidence: 99%

Coupling pre-mRNA processing to transcription on the RNA factory assembly line

Lee

Tarn

2013

RNA Biology

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Identification and functional analysis ofSOX10missense mutations in different subtypes of waardenburg syndrome

et al. 2011

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Waardenburg syndrome (WS) is a rare disorder characterized by pigmentation defects and sensorineural deafness, classified into four clinical subtypes, WS1-S4. Whereas the absence of additional features characterizes WS2, association with Hirschsprung disease defines WS4. WS is genetically heterogeneous, with six genes already identified, including SOX10. About 50 heterozygous SOX10 mutations have been described in patients presenting with WS2 or WS4, with or without myelination defects of the peripheral and central nervous system (PCWH, Peripheral demyelinating neuropathy-Central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease, or PCW, PCWH without HD). The majority are truncating mutations that most often remove the main functional domains of the protein. Only three missense mutations have been thus far reported. In the present study, novel SOX10 missense mutations were found in 11 patients and were examined for effects on SOX10 characteristics and functions. The mutations were associated with various phenotypes, ranging from WS2 to PCWH. All tested mutations were found to be deleterious. Some mutants presented with partial cytoplasmic redistribution, some lost their DNA-binding and/or transactivation capabilities on various tissue-specific target genes. Intriguingly, several mutants were redistributed in nuclear foci. Whether this phenomenon is a cause or a consequence of mutation-associated pathogenicity remains to be determined, but this observation could help to identify new SOX10 modes of action.

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

Cited by 77 publications

References 33 publications

Sox9 Family Members Negatively Regulate Maturation and Calcification of Chondrocytes through Up-Regulation of Parathyroid Hormone–related Protein

Sox9 Family Members Negatively Regulate Maturation and Calcification of Chondrocytes through Up-Regulation of Parathyroid Hormone–related Protein

Coupling pre-mRNA processing to transcription on the RNA factory assembly line

Identification and functional analysis ofSOX10missense mutations in different subtypes of waardenburg syndrome

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