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A GG nucleotide sequence of the 3' untranslated region of amyloid precursor protein mRNA plays a key role in the regulation of translation and the binding of proteins.

机译:淀粉样前体蛋白mRNA 3'非翻译区的GG核苷酸序列在蛋白质的翻译和结合调节中起关键作用。

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摘要

The alternative polyadenylation of the mRNA encoding the amyloid precursor protein (APP) involved in Alzheimer's disease generates two molecules, with the first of these containing 258 additional nucleotides in the 3' untranslated region (3'UTR). We have previously shown that these 258 nucleotides increase the translation of APP mRNA injected in Xenopus oocytes (5). Here, we demonstrate that this mechanism occurs in CHO cells as well. We also present evidence that the 3'UTR containing 8 nucleotides more than the short 3'UTR allows the recovery of an efficiency of translation similar to that of the long 3'UTR. Moreover, the two guanine residues located at the 3' ends of these 8 nucleotides play a key role in the translational control. Using gel retardation mobility shift assay, we show that proteins from Xenopus oocytes, CHO cells, and human brain specifically bind to the short 3'UTR but not to the long one. The two guanine residues involved in the translational control inhibit this specific binding by 65%. These results indicate that there is a correlation between the binding of proteins to the 3'UTR of APP mRNA and the efficiency of mRNA translation, and that a GG motif controls both binding of proteins and translation.
机译:编码与阿尔茨海默氏病有关的淀粉样蛋白前体蛋白(APP)的mRNA的另一种聚腺苷酸化作用产生了两个分子,其中第一个在3'非翻译区(3'UTR)中包含258个附加核苷酸。我们先前已经表明,这258个核苷酸增加了非洲爪蟾卵母细胞中注射的APP mRNA的翻译(5)。在这里,我们证明了这种机制也发生在CHO细胞中。我们还提供了证据,即比短3'UTR多包含8个核苷酸的3'UTR允许恢复与长3'UTR相似的翻译效率。此外,位于这8个核苷酸的3'末端的两个鸟嘌呤残基在翻译控制中起关键作用。使用凝胶阻滞迁移率位移测定法,我们显示来自非洲爪蟾卵母细胞,CHO细胞和人脑的蛋白质特异性结合短的3'UTR,但不结合长的3'UTR。参与翻译控制的两个鸟嘌呤残基将这种特异性结合抑制了65%。这些结果表明,蛋白质与APP mRNA的3'UTR的结合与mRNA翻译的效率之间存在相关性,并且GG基序既控制蛋白质的结合又控制翻译。

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