Nucleic Acids Research, 2000, Vol. 28, No. 2 641-647
© 2000 Oxford University Press
The 5' stem–loop regulates expression of collagen 
1(I) mRNA in mouse fibroblasts cultured in a three-dimensional matrix
Departments of Medicine and Biochemistry and Biophysics, University of North Carolina at Chapel Hill, CB 7038, Chapel Hill, NC 27599, USA
The stability of collagen 
1(I) mRNA is regulated by its 5' stem–loop, which binds a cytoplasmic protein in a cap-dependent manner, and its 3'-untranslated region (UTR), which binds CP. When cultured in a three-dimensional gel composed of type I collagen, mouse fibroblasts had decreased collagen 1(I) mRNA steady-state levels, which resulted from a decreased mRNA half-life. In cells cultured in gel, hybrid mouse–human collagen 1(I) mRNA with a wild-type 5' stem–loop decayed faster than the same mRNA with a mutated stem–loop. When the 5' stem–loop was placed in a heterologous mRNA, the mRNA accumulated to a lower level in cells grown in gel than in cells grown on plastic. This suggests that the 5' stem–loop down-regulates collagen 1(I) mRNA. Protein binding to the 5' stem–loop was reduced in cells grown in gel, which was associated with destabilization of the collagen 1(I) mRNA. In addition to the binding of a cytoplasmic protein, there was also a nuclear binding activity directed to the collagen 1(I) 5' stem–loop. The nuclear binding was increased in cells grown in gel, suggesting that it may negatively regulate expression of collagen 1(I) mRNA. Binding of CP, a protein involved in stabilization of collagen 1(I) mRNA, was unchanged by the culture conditions.
* To whom correspondence should be addressed. Tel: +1 919 966 7885; Fax: +1 919 966 7468; Email: dab@med.unc.edu
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