Formation of DNA:RNA Hybrid G-Quadruplexes of Two G-Quartet Layers in Transcription: Expansion of the Prevalence and Diversity of G-Quadruplexes in Genomes

G‐quadruplexes are implicated in important cellular processes. Previous studies mostly focused on intramolecular G‐quadruplexes of three or more G‐quartets. Those composed of two G‐quartets were only shown to form in single‐stranded oligonucleotides. On the basis of electrophoresis, DMS footprinting...

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Published in:Angewandte Chemie International Edition 2014-11, Vol.53 (48), p.13110-13114
Main Authors: Xiao, Shan, Zhang, Jia-yu, Wu, Jun, Wu, Ren-yi, Xia, Ye, Zheng, Ke-wei, Hao, Yu-hua, Zhou, Xiang, Tan, Zheng
Format: Article
Language:English
Subjects:
Control
Deoxyribonucleic acid
DNA
DNA - genetics
Expansion
Formations
G-quadruplexes
G-Quadruplexes - drug effects
Genes
Genome - genetics
Genomes
Human
Humans
Ligands
Oligonucleotides
Oligonucleotides - genetics
Prevalence
Ribonucleic acids
RNA
RNA - genetics
transcription
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Summary:G‐quadruplexes are implicated in important cellular processes. Previous studies mostly focused on intramolecular G‐quadruplexes of three or more G‐quartets. Those composed of two G‐quartets were only shown to form in single‐stranded oligonucleotides. On the basis of electrophoresis, DMS footprinting, fluorescence labeling, and photo‐cross‐linking, we detected the formation of DNA:RNA hybrid G‐quadruplexes (HQs) of two G‐quartets during the transcription of DNA duplexes. These HQs have a lifetime on the minute scale and are stabilized by a stabilizing ligand. They are far shorter‐lived than the HQs of three G‐quartets, which last for hours. The occurrence of putative formation motifs of such HQs shows a transcription‐dependent strand‐biased selection, thus supporting their formation and function in genomes. They are present in almost all human genes in large amounts. We speculate that the two‐G‐quartet HQs may be a distinct type of G‐quadruplexes that may play a role in timely responsive processes and for purposes of fine‐tuning. Quartets unite to call the tune: The transcription of G‐rich DNA produces G‐rich RNA transcripts. G‐tracts from DNA and RNA were found to form hybrid G‐quadruplexes (HQs) of two or more G‐quartets (see picture) with a possible role in transcription regulation. DNA:RNA HQs composed of two G‐quartets were less stable and more flexible than HQs composed of three G‐quartets, and their folding and unfolding were more responsive to transcription activity.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201407045