MTG8 (RUNX1T1) is a fusion partner of AML1 (RUNX1) in the leukemic chromosome translocation t(8;21). The AML1‐MTG8 fusion gene encodes a chimeric transcription factor. One of the highly conserved domains of MTG8 is TAFH which possesses homology with human TAF4 [TATA‐box binding protein‐associated factor]. To obtain specific inhibitors of the AML1‐MTG8 fusion protein, we isolated RNA aptamers against the MTG8 TAFH domain using systematic evolution of ligands by exponential enrichment. All TAF aptamers contained guanine‐rich sequences. Analyses of a TAF aptamer by NMR, CD, and mutagenesis revealed that it forms a parallel G‐quadruplex structure in the presence of K+. Furthermore, the aptamer could bind to the AML1‐MTG8 fusion protein and dissociate the AML1‐MTG8/DNA complex, suggesting that it can inhibit the dominant negative effects of AML1‐MTG8 against normal AML1 function and serve as a potential therapeutic agent for leukemia.

中文翻译：

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形成AG-四链体的RNA适体结合MTG8 TAFH结构域并将白血病AML1-MTG8融合蛋白与DNA分离

MTG8 (RUNX1T1) 是 AML1 (RUNX1) 在白血病染色体易位 t(8;21) 中的融合伙伴。AML1-MTG8 融合基因编码嵌合转录因子。MTG8 的高度保守结构域之一是 TAFH，它与人 TAF4 [TATA-box 结合蛋白相关因子]具有同源性。为了获得 AML1-MTG8 融合蛋白的特异性抑制剂，我们通过指数富集的配体系统进化，分离了针对 MTG8 TAFH 结构域的 RNA 适配体。所有 TAF 适配体都含有富含鸟嘌呤的序列。通过 NMR、CD 和诱变对 TAF 适体进行分析表明，它在 K+ 存在下形成平行的 G-四链体结构。此外，适体可以与 AML1-MTG8 融合蛋白结合并解离 AML1-MTG8/DNA 复合物，