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首页> 外文期刊>Biochemistry >Repression of Translation of Human Estrogen Receptor α by G-Quadruplex Formation
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Repression of Translation of Human Estrogen Receptor α by G-Quadruplex Formation

机译:G-四链体形成抑制人雌激素受体α的翻译

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摘要

Tissue-specific expression of the human estrogen receptor R gene (ESR1) is achieved throughnmultiple promoter sequences resulting in variousmRNAtranscripts encoding a common protein but differing inntheir 50n-untranslated region (50n-UTR). Many cancers are estrogen-sensitive with neoplastic growth stimulatednthrough the estrogen receptor, a transcription factor that regulates developmental genes. We demonstrate thatnthe human ESR1 gene is rich in potential quadruplex-forming sequences with 3 of 20 identified within exonicnregions. In particular,we showusingCD,UV, andNMRspectroscopy that a stableDNAG-quadruplexmotif isnformed within the exon C gene sequence. This motif, which PCR shows is transcribed in normal and neoplasticnendometrium and in MCF-7 cells, forms a stable RNA quadruplex demonstrable by CD and UV analysis.nCloning the exon C G-quadruplex sequence upstream of a luciferase reporter gene caused a 6-fold reduction ofnenzymatic activity compared to a mutant sequence.We conclude that the exon C G-quadruplex motif is presentnin the 50n-UTR of the mRNA transcript, where it modulates the efficiency of translation.
机译:人类雌激素受体R基因(ESR1)的组织特异性表达是通过多个启动子序列实现的,从而导致编码共同蛋白但在其50n非翻译区(50n-UTR)不同的各种mRNA转录本。许多癌症对雌激素敏感,并通过调节发育基因的转录因子雌激素受体刺激肿瘤生长。我们证明,人类ESR1基因富含潜在的四链体形成序列,在外显子区域内鉴定出20个中的3个。特别是,我们使用CD,UV和NMR光谱表明在外显子C基因序列中形成了稳定的DNAG-四链基序。 PCR显示该基序在正常和赘生性子宫内膜以及MCF-7细胞中转录,形成了可通过CD和UV分析证实的稳定的RNA四链体。n将萤光素酶报告基因上游的外显子C G-四链体序列克隆导致6倍与突变序列相比,酶活性降低。我们得出结论,外显子C G-四链体基序存在于mRNA转录本的50n-UTR中,在其中调节翻译效率。

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