Adenosine-uridine binding factor requires metals for binding to granulocyte-macrophage colony-stimulating factor mRNA.

Adenosine-uridine binding factor requires metals for binding to granulocyte-macrophage colony-stimulating factor mRNA.
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腺苷-尿苷结合因子需要金属来与粒细胞-巨噬细胞集落刺激因子 mRNA 结合。

DOI:
10.1159/000468758
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发表时间:
1990
期刊:
Enzyme
影响因子:
--
通讯作者:
Gillis,P
Gillis,P
中科院分区:
--
文献类型:
--
作者:
Malter,JS;McCrory,WA;Wilson,M;Gillis,P

文献摘要

被引文献

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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显著稳定。GM-CSF和其他不稳定mRNA的3 '非翻译区含有去稳定基序腺苷-尿苷-腺苷(AUUUA)。我们最近发现了一种细胞质蛋白,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转录物中的AUUUA元件结合。我们现在证明,AUBF特异性结合GM-CSF mRNA通过不稳定的AUUUA元件。AUBF-GM-CSFRNA复合物的形成需要钙或镁,而钙或镁对EDTA或EGTA敏感。多种其他二价金属阻断镁依赖性AUBF活性。这些观察结果表明,AUBF可以保护GM-CSF mRNA的快速降解,并在细胞因子基因的表达中起着至关重要的作用。
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.