Posttranscriptional regulation of chicken ccn2 gene expression by nucleophosmin/B23 during chondrocyte differentiation.
CCN2/CTGF is a multifunctional factor that plays a crucial role in the growth and differentiation of chondrocytes. The chicken ccn2 gene is regulated not only at the transcriptional level but also by the interaction between a posttranscriptional element in the 3' untranslated region (3'-UTR) and a cofactor. In the present study, we identified a nucleophosmin (NPM) (also called B23) as this cofactor. Binding of NPM to the element was confirmed, and subsequent analysis revealed a significant correlation between the decrease in cytosolic NPM and the increased stability of the ccn2 mRNA during chondrocyte differentiation in vivo. Furthermore, recombinant chicken NPM enhanced the degradation of chimeric RNAs containing the posttranscriptional cis elements in a chicken embryonic fibroblast extract in vitro. It is noteworthy that the RNA destabilization effect by NPM was far more prominent in the cytosolic extract of chondrocytes than in that of fibroblasts, representing a chondrocyte-specific action of NPM. Stimulation by growth factors to promote differentiation changed the subcellular distribution of NPM in chondrocytes, which followed the expected patterns from the resultant change in the ccn2 mRNA stability. Therefore, the present study reveals a novel aspect of NPM as a key player in the posttranscriptional regulation of ccn2 mRNA during the differentiation of chondrocytes.
Mukudai
Yoshiki
Y
Biodental Research Center, Okayama University Dental School, Okayama 700-8525, Japan.
Kubota
Satoshi
S
Kawaki
Harumi
H
Kondo
Seiji
S
Eguchi
Takanori
T
Sumiyoshi
Kumi
K
Ohgawara
Toshihiro
T
Shimo
Tsuyoshi
T
Takigawa
Masaharu
M
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D002645:Chickens; D020219:Chondrogenesis; D055513:Connective Tissue Growth Factor; D004625:Embryo, Nonmammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin
D020413:3' Untranslated Regions; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D055513:Connective Tissue Growth Factor