Malter J S, McCrory W A, Wilson M, Gillis P
Department of Pathology, Tulane University School of Medicine, New Orleans, La.
Enzyme. 1990;44(1-4):203-13. doi: 10.1159/000468758.
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.
转录后基因调控在粒细胞-巨噬细胞集落刺激因子（GM-CSF）的表达中起重要作用。活化的淋巴细胞或肥大细胞分泌细胞因子之前，通常不稳定的GM-CSF mRNA会显著稳定。GM-CSF和其他不稳定mRNA的3'非翻译区含有去稳定化基序腺苷-尿苷-尿苷-尿苷-腺苷（AUUUA）。我们最近鉴定出一种细胞质蛋白，称为腺苷-尿苷结合因子（AUBF），它以高亲和力和特异性与合成RNA转录本中的AUUUA元件结合。我们现在证明AUBF通过去稳定化的AUUUA元件特异性结合GM-CSF mRNA。AUBF-GM-CSF RNA复合物的形成需要钙或镁，而它们对EDTA或EGTA敏感。多种其他二价金属会阻断镁依赖性的AUBF活性。这些观察结果表明，AUBF可能保护GM-CSF mRNA免于快速降解，并在细胞因子基因的表达中起关键作用。
