Characterization of two nuclear proteins that interact with cytochrome P-450 1A2 mRNA - Regulation of RNA binding and possible role in the expression of the Cyp1a2 gene

Raffalli- Mathieu, Francoise, Geneste, Olivier and Lang, Matti A. (1997) Characterization of two nuclear proteins that interact with cytochrome P-450 1A2 mRNA - Regulation of RNA binding and possible role in the expression of the Cyp1a2 gene. European Journal of Biochemistry, 245 1: 17-24. doi:10.1111/j.1432-1033.1997.00017.x


Author Raffalli- Mathieu, Francoise
Geneste, Olivier
Lang, Matti A.
Title Characterization of two nuclear proteins that interact with cytochrome P-450 1A2 mRNA - Regulation of RNA binding and possible role in the expression of the Cyp1a2 gene
Journal name European Journal of Biochemistry   Check publisher's open access policy
ISSN 0014-2956
1432-1033
Publication date 1997-04
Sub-type Article (original research)
DOI 10.1111/j.1432-1033.1997.00017.x
Volume 245
Issue 1
Start page 17
End page 24
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Regulation of the expression of the cytochrome P-450 1a2 gene (cyp1a2) occurs mainly at the transcriptional level, but the molecular events involved in the induction process are partly unknown. Some reports have proposed involvement of post-transcriptional mechanisms [Adesnik, M. and Atchison, M. (1986) Crit. Rev. Biochem. 19, 247-305; Silver, G. and Krauter, K.S. (1990) Mol. Cell. Biol. 10, 6765-6768]. Here we report the identification of two proteins in the nuclear fraction of mouse liver, with specific binding characteristics towards CYP1A2 mRNA. The proteins have apparent molecular masses of 37 kDa and 46 kDa and exhibit a high affinity for a poly(U) motif in the 3' untranslated region of CYP1A2 mRNA; This motif seems to be important for their specific and apparently competitive binding to CYP1A2 mRNA. Treatment of mice with an inducer of CYP1A2, 3-methylcholanthrene, increases the binding of the 46-kDa protein and decreases the binding of the 37-kDa protein to the mRNA, suggesting that changes in the binding of the proteins to the mRNA could play a role in the upregulation of CYP1A2 mRNA by 3-methylcholanthrene. Phosphorylation of the 46-kDa protein, or of an intermediary factor, may play a role in its binding activity. Furthermore, the 46-kDa but not the 37-kDa protein is recognized by a monoclonal antibody against the heterogeneous nuclear ribonucleoprotein C, a nuclear protein probably involved in pre-mRNA processing. While more work is needed to understand the function of the proteins that bind to the 3' untranslated region of CYP1A2, it is possible that the 37-kDa protein has a role in the maintenance of uninduced levels of CYP1A2 mRNA, while the 46-kDa protein could be important in the maturation of elevated levels of CYP1A2 pre-mRNA, during induction.
Keyword Cytochrome P-450 1A2
RNA-binding protein
3' untranslated region
Induction
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Continues (2005-)- The FEBS Journal (1742-4658; 1742-464X)

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Mon, 30 Nov 2009, 15:07:45 EST