Translational enhancement of H-ferritin mRNA by interleukin-1 beta acts through 5' leader sequences distinct from the iron responsive element.
Interleukin-1 beta (Il-1 beta), a key cytokine in the acute phase response, elevates hepatic expression of both the heavy (H) and light (L) ferritin subunits without influencing the steady-state levels of either ferritin transcript. Transfection experiments with human hepatoma cells reveal that sequences within the 5' untranslated region (5'UTR) of H-ferritin mRNA confer translational regulation to chimaeric chloramphenicol acetyl transferase (CAT) mRNAs in response to Il-1 beta in the absence of marked changes in CAT mRNA levels. Il-1 beta dependent translational enhancement is mediated by a distinct G + C rich RNA sequence within 70 nucleotides (nt) of the start codon. The upstream Iron Responsive Element RNA stemloop does not confer increased expression to CAT mRNA in Il-1 beta stimulated hepatoma transfectants. A 38 nucleotide consensus sequence within the 5'UTRs of the mRNAs encoding the hepatic acute phase proteins alpha 1-antitrypsin (alpha 1AT), alpha 1-acid glycoprotein (AGP) and haptoglobin (Dente et al., 1985) is similar to sequences in the G + C rich H-ferritin mRNA translational regulatory element. Deletion of three nucleotides from this region of the 61 nt G + C rich element in the H-ferritin mRNA 5' leader eliminates Il-1 beta translational enhancement of the CAT reporter transcripts.
Rogers
J T
JT
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Andriotakis
J L
JL
Lacroix
L
L
Durmowicz
G P
GP
Kasschau
K D
KD
Bridges
K R
KR
D001483:Base Sequence; D016384:Consensus Sequence; D004247:DNA; D005293:Ferritins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D012333:RNA, Messenger; D004247:DNA; D005293:Ferritins; D007501:Iron