FERRITIN TRANSLATION BY INTERLEUKIN-1 AND INTERLEUKIN-6 - THE ROLE OFSEQUENCES UPSTREAM OF THE START CODONS OF THE HEAVY AND LIGHT SUBUNITGENES

Interleukin-1 beta (IL-1 beta) elevates H- and L-ferritin subunit synt hesis in both human hepatoma cells (HepG2) and primary human umbilical vein endothelial cells. Ferritin induction is greater than the increa se in total HepG2 protein synthesis in response to IL-1. IL-6 causes a moderate increase in L-subunit synthesis. The levels of the mRNAs for the ferritin H-subunits (H-mRNA) and light subunits (L-mRNA) remain u nchanged, indicating that expression of the iron storage protein. ferr itin, is regulated by translational mechanisms during inflammation. We have found a translational enhancer region in the L-ferritin mRNA 5'U TR that confers twofold baseline and twofold IL-1-dependent translatio nal regulation to a CAT reporter message. The L-mRNA motif is related to a 61 nucleotide (nt) G+C-rich translational enhancer within 70 nt o f the H-ferritin start codon. Sequences upstream of the start codons ( SUS elements) in both H-mRNA and L-mRNAs confer IL-1 beta- but not IL- 6-dependent translation to hybrid ferritin/CAT reporter mRNAs. The H- and L-ferritin mRNA SUS elements contain a motif similar to a consensu s reported for the 5' leaders of other acute-phase response mRNAs. Tra nsfected hybrid H-mRNA SUS/CAT mRNAs with a three nucleotide deleted v ersion of the H-mRNA SUS displays an eightfold reduced level of transl ation and no longer confer IL-1 beta-dependent translation. (C) 1996 b y The American Society of Hematology.