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In vitro up‐regulation of ferritin expression mediated by small molecules that target mRNA
Author(s) -
Sullivan Julie M,
Ropp Patricia A.,
Thorp H. Holden,
Theil Elizabeth C.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a281
Subject(s) - ferritin , chemistry , messenger rna , untranslated region , small molecule , in vitro , promazine , microbiology and biotechnology , translation (biology) , downregulation and upregulation , gene , biochemistry , biology , chlorpromazine , endocrinology
The targeting of specific structural elements in mRNA with small molecules has become a promising method for regulating gene expression. One such target is the iron‐responsive element (IRE) found in the human ferritin gene. The translation of ferritin mRNA is controlled by the binding of two iron regulatory proteins (IRPs) to a hairpin structure found in the non‐coding 5′UTR. We have previously utilized an oxidizing metal complex (Ru(tpy)(bpy)O 2+ ) to identify small molecules that bind specifically and selectively to the IRE sequence. Two small molecules, yohimbine and promazine bind to the internal bulge in the IRE hairpin structure, blocking the interactions of IRPs with the ferritin mRNA. The binding constants for the small molecule: IRE interaction are in the low micromolar range. In vitro translation assays show that ferritin production is upregulated in the presence of both yohimbine and promazine.