Regulation of macrophage ceruloplasmin gene expression: one paradigm of 3'-UTR-mediated translational control.
Ceruloplasmin (Cp) is a copper protein with important functions in iron homeostasis and in inflammation. Cp mRNA expression is induced by interferon (IFN)-g in U937 monocytic cells, but synthesis of Cp protein is halted after about 12 h by transcript-specific translational silencing. The silencing mechanism requires binding of a 4-component cytosolic inhibitor complex, IFN-gamma-activated inhibitor of translation (GAIT), to a defined structural element (GAIT element) in the Cp 3'-UTR. Translational silencing of Cp mRNA requires the essential proteins of mRNA circularization, suggesting that the translational inhibition requires end-to-end mRNA closure. These studies describe a new mechanism of translational control, and may shed light on the role that macrophage-derived Cp plays at the intersection of iron homeostasis and inflammation.
Mazumder
Barsanjit
B
Department of Biology, Geology, and Environmental Sciences, Cleveland State University, Cleveland, OH, USA.
Sampath
Prabha
P
Fox
Paul L
PL
D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002570:Ceruloplasmin / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D012333:RNA, Messenger; D002570:Ceruloplasmin