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The regulation and functions of DNA and RNA G-quadruplexes.
Nature Reviews Molecular Cell Biology ( IF 112.7 ) Pub Date : 2020-04-20 , DOI: 10.1038/s41580-020-0236-x
Dhaval Varshney 1 , Jochen Spiegel 1 , Katherine Zyner 1 , David Tannahill 1 , Shankar Balasubramanian 1, 2, 3
Affiliation  

DNA and RNA can adopt various secondary structures. Four-stranded G-quadruplex (G4) structures form through self-recognition of guanines into stacked tetrads, and considerable biophysical and structural evidence exists for G4 formation in vitro. Computational studies and sequencing methods have revealed the prevalence of G4 sequence motifs at gene regulatory regions in various genomes, including in humans. Experiments using chemical, molecular and cell biology methods have demonstrated that G4s exist in chromatin DNA and in RNA, and have linked G4 formation with key biological processes ranging from transcription and translation to genome instability and cancer. In this Review, we first discuss the identification of G4s and evidence for their formation in cells using chemical biology, imaging and genomic technologies. We then discuss possible functions of DNA G4s and their interacting proteins, particularly in transcription, telomere biology and genome instability. Roles of RNA G4s in RNA biology, especially in translation, are also discussed. Furthermore, we consider the emerging relationships of G4s with chromatin and with RNA modifications. Finally, we discuss the connection between G4 formation and synthetic lethality in cancer cells, and recent progress towards considering G4s as therapeutic targets in human diseases.

中文翻译:

DNA和RNA G-四链体的调控和功能。

DNA和RNA可以采用各种二级结构。四链 G-四链体 (G4) 结构通过鸟嘌呤的自我识别形成堆叠的四分体,并且存在大量的生物物理和结构证据表明 G4 在体外形成。计算研究和测序方法揭示了 G4 序列基序在包括人类在内的各种基因组的基因调控区的普遍存在。使用化学、分子和细胞生物学方法的实验表明,G4 存在于染色质 DNA 和 RNA 中,并将 G4 的形成与从转录和翻译到基因组不稳定性和癌症的关键生物过程联系起来。在这篇综述中,我们首先使用化学生物学、成像和基因组技术讨论 G4 的鉴定及其在细胞中形成的证据。然后,我们讨论了 DNA G4 及其相互作用蛋白的可能功能,特别是在转录、端粒生物学和基因组不稳定性方面。还讨论了 RNA G4 在 RNA 生物学中的作用,特别是在翻译中的作用。此外,我们考虑 G4s 与染色质和 RNA 修饰的新兴关系。最后,我们讨论了 G4 形成与癌细胞合成致死率之间的联系,以及将 G4 作为人类疾病治疗靶点的最新进展。
更新日期:2020-04-24
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