State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (P.R. China).
Angew Chem Int Ed Engl. 2015 Feb 16;54(8):2447-51. doi: 10.1002/anie.201408719. Epub 2015 Jan 22.
DNA with four guanine tracts can fold into G-quadruplexes that are targets of transcription regulation. We recently found that hybrid DNA:RNA G-quadruplexes (HQs) can form during in vitro transcription. However, it is unclear whether they can form in cells. Evidence is presented supporting their formation in plasmids in bacterial cells. The formation of the HQs is indicated by a unique pattern of prematurely terminated transcripts under two conditions where the RNA transcripts do or do not participate in G-quadruplex assembly and further supported by a number of chemical and biochemical analysis. HQs dominate over the intramolecular DNA G-quadruplexes (DQ) in mediating the transcription termination when both structures are able to form. These findings provide the first evidence of HQ formation in cells and suggest that the competition/conversion between HQ and DQ may regulate transcription and serve as drug target in pharmaceutical applications.
具有四个鸟嘌呤（G）碱基链段的 DNA 可以折叠成 G-四链体，后者是转录调控的靶标。我们最近发现，在体外转录过程中可以形成杂交 DNA:RNA G-四链体 (HQ)。然而，目前尚不清楚它们是否能在细胞中形成。有证据表明它们可以在细菌细胞的质粒中形成。HQ 的形成是通过两种情况下 RNA 转录本是否参与 G-四链体组装的独特的过早终止转录本模式来指示的，并且进一步得到了一些化学和生化分析的支持。当两种结构都能够形成时，HQ 主导着介导转录终止的分子内 DNA G-四链体 (DQ)。这些发现提供了 HQ 在细胞中形成的首个证据，并表明 HQ 和 DQ 之间的竞争/转换可能调节转录，并可作为药物靶点在药物应用中使用。
