Adenosine-uridine binding factor requires metals for binding to granulocyte-macrophage colony-stimulating factor mRNA.
Post-transcriptional gene regulation plays an important role in the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF). Cytokine secretion by activated lymphocytes or mast cells is preceded by dramatic stabilization of the normally labile GM-CSF mRNA. The 3'-untranslated region of GM-CSF and other labile mRNAs contain the destabilizing motif adenosine-uridine-uridine-uridine-adenosine (AUUUA). We recently identified a cytoplasmic protein denoted the adenosine-uridine binding factor (AUBF) which binds with high affinity and specificity to AUUUA elements in synthetic RNA transcripts. We now demonstrate that AUBF binds specifically to GM-CSF mRNA through the destabilizing AUUUA elements. The formation of AUBF-GM-CSF RNA complexes required calcium or magnesium which were sensitive to EDTA or EGTA. A variety of other divalent metals blocked magnesium-dependent AUBF activity. These observations suggest that AUBF may protect GM-CSF mRNA from rapid degradation and play a crucial role in the expression of cytokine genes.
Malter
J S
JS
Department of Pathology, Tulane University School of Medicine, New Orleans, La.
McCrory
W A
WA
Wilson
M
M
Gillis
P
P
D000818:Animals; D002413:Cations, Divalent / Q000378:metabolism*; D002478:Cells, Cultured; D004492:Edetic Acid; D004533:Egtazic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D008214:Lymphocytes / Q000166:cytology; D008670:Metals / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*
D002413:Cations, Divalent; D008670:Metals; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D004533:Egtazic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004492:Edetic Acid