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Guanine-Tethered Oligonucleotides Restore Abnormal Protein Synthesis with a SNP Mutation in a 5’-UTR G-quadruplex of Human MSH2
Chemistry Letters ( IF 1.6 ) Pub Date : 2021-07-21 , DOI: 10.1246/cl.210391
Masaki Hagihara 1 , Shuhei Shiroto 1 , Shunya Igarashi 1 , Shin-ichi Sato 2
Affiliation  

Here we demonstrate that a guanine-to-adenine substitution within guanine repeat sequences in the MSH 5’-UTR weakens G-quadruplex stability, leading to increased protein synthesis. The abnormal protein synthesis was effectively restored to the original level with a guanine-tethered oligonucleotide by the sequence-specific reintroduction of a hetero RNA–DNA G-quadruplex into the SNP site of the 5’ UTR of MSH2. Our approach would provide a new insight into gene therapies for various diseases which are caused by gene mutations in biological relevant G-quadruplexes.

中文翻译:

鸟嘌呤系留寡核苷酸通过人 MSH2 的 5'-UTR G-四链体中的 SNP 突变恢复异常蛋白质合成

在这里,我们证明 MSH 5'-UTR 中鸟嘌呤重复序列内的鸟嘌呤到腺嘌呤替代削弱了 G-四链体的稳定性,从而导致蛋白质合成增加。通过将异源 RNA-DNA G-四链体序列特异性重新引入 MSH2 5' UTR 的 SNP 位点,将异常的蛋白质合成有效地恢复到原始水平。我们的方法将为各种疾病的基因治疗提供新的见解,这些疾病是由生物相关 G-四链体中的基因突变引起的。
更新日期:2021-07-21
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