Cytochrome P450 RNA—Protein Interactions
Humans are constantly exposed to xenobiotics present in the environment, the food, or from clinical use. To counteract the toxic accumulation of foreign molecules, living organisms have evolved a defense system comprising a family of detoxifying enzymes (cytochromes P450, CYPs). Numerous xenobiotics induce CYP genes: the induction is an essential adaptive mechanism that allows organisms to adjust their detoxification capacity according to the needs. Only in a few cases are the induction mechanisms understood to some extent. While it is well admitted that both transcriptional and post-transcriptional (mRNA processing and turnover) control is important for cyp genes expression, very little is known about the post-transcriptional mechanisms Of regulation. We have investigated the post-transcriptional regulation of two CYP genes, CYP1A2 and CYP2A5, and identified RNA-binding proteins interacting with their mRNA in an inducer-dependent manner. The strategy used to characterize the RNA protein interaction and to identify the relevant RNA sequences as well as the regulatory factors are described in this chapter.
KeywordsElectrophoretic Mobility Shift Assay CYP2A5 mRNA Posttranscriptional Regulation Homeostatic Regulation Heterogeneous Nuclear Ribonucleoprotein
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- 1.Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, CoonMJ, Estabrook RW, Gunsalus IC, Nebert DW. 1996 P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics. 6 (1): 1–42Google Scholar
- 5.Zubiaga AM, Belasco JG, Greenberg ME. 1995 The nonamer UUAUUUAUU is the key AU-rich sequence motif that mediates mRNA degradation. Mol Cell Biol. 15(4): 221930.Google Scholar
- 6.SiomiH, Dreyfuss G. 1997 RNA-binding proteins as regulators of gene expression. Curr Opin Genet Dev. 7(3):345–53. Review.Google Scholar
- 7.Krecic AM, Swanson MS. 1999 hnRNP complexes: composition, structure, and function. Curr Opin Cell Biol. 11(3):363–71Google Scholar
- 22.Pasco DS, Boyum KW, Merchant SN, Chalberg SC, Fagan JB. 1988 Transcriptional and post-transcriptional regulation of the genes encoding cytochromes P-450c and P-450d in vivo and in primary hepatocyte cultures. J Biol Chem. 263 (18): 8671–6.Google Scholar
- 27.Roy NK, Kreamer GL, Konkle B, Grunwald C, Wirgin I. C1995 haracterization and prevalence of a polymorphism in the 3’ untranslated region of cytochrome P4501Alin cancer-prone Atlantic tomcod. Arch Biochem Biophys. 322(1):204–13.Google Scholar