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新型 STAT3 基因 G-四链体的形成、识别及生物活性。

Formation, recognition and bioactivities of a novel G-quadruplex in the STAT3 gene.

机构信息

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

出版信息

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5987-91. doi: 10.1016/j.bmcl.2011.07.121. Epub 2011 Aug 6.

DOI:10.1016/j.bmcl.2011.07.121
PMID:21873055
Abstract

G-Quadruplexes have been proved to exist in 5'-untranslated region (5'-UTR), promoter, intron and exon regions of many human genes. Here we report an intramolecular G-quadruplex formed by a G-rich sequence in the 3'-flanking region of signal transducers and activators of transcription 3 (STAT3) gene. The results showed that this G-rich sequence could affect the expression of STAT3. When the STAT3 G-quadruplex was stabilized by a novel non-planar ligand Cepharanthine (CEP), the decreased expression of STAT3 was observed in primary cultured cardiomyocytes. We also demonstrated that the down-regulation of STAT3 was most likely occurred at the transcriptional level. Our results provide a new clue for studying the G-quadruplex formation, recognition and function in the 3'-flanking region of gene.

摘要

G-四链体已被证明存在于许多人类基因的 5'-非翻译区(5'-UTR)、启动子、内含子和外显子区域。在这里,我们报告了一个由信号转导和转录激活因子 3(STAT3)基因 3'侧翼区富含 G 的序列形成的分子内 G-四链体。结果表明,该富含 G 的序列可能影响 STAT3 的表达。当新型非平面配体 Ceparanthine(CEP)稳定 STAT3 G-四链体时,原代培养的心肌细胞中观察到 STAT3 的表达降低。我们还表明,STAT3 的下调很可能发生在转录水平。我们的研究结果为研究基因 3'侧翼区 G-四链体的形成、识别和功能提供了新的线索。

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