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Title: Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study
Authors: Lim, Kah Wai
Jenjaroenpun, Piroon
Low, Zhen Jie
Khong, Zi Jian
Ng, Yi Siang
Kuznetsov, Vladimir Andreevich
Phan, Anh Tuan
Keywords: Physics & Applied Physics
Biological Sciences
Issue Date: 2015
Source: Lim, K. W., Jenjaroenpun, P., Low, Z. J., Khong, Z. J., Ng, Y. S., Kuznetsov, V. A., et al. (2015). Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study. Nucleic Acids Research, 43(11), 5630-5646.
Series/Report no.: Nucleic Acids Research
Abstract: Duplex stem-loops and four-stranded G-quadruplexes have been implicated in (patho)biological processes. Overlap of stem-loop- and quadruplex-forming sequences could give rise to quadruplex–duplex hybrids (QDH), which combine features of both structural forms and could exhibit unique properties. Here, we present a combined genomic and structural study of stem-loop-containing quadruplex sequences (SLQS) in the human genome. Based on a maximum loop length of 20 nt, our survey identified 80 307 SLQS, embedded within 60 172 unique clusters. Our analysis suggested that these should cover close to half of total SLQS in the entire genome. Among these, 48 508 SLQS were strand-specifically located in genic/promoter regions, with the majority of genes displaying a low number of SLQS. Notably, genes containing abundant SLQS clusters were strongly associated with brain tissues. Enrichment analysis of SLQS-positive genes and mapping of SLQS onto transcriptional/mutagenesis hotspots and cancer-associated genes, provided a statistical framework supporting the biological involvements of SLQS. In vitro formation of diverse QDH by selective SLQS hits were successfully verified by nuclear magnetic resonance spectroscopy. Folding topologies of two SLQS were elucidated in detail. We also demonstrated that sequence changes at mutation/single-nucleotide polymorphism loci could affect the structural conformations adopted by SLQS. Thus, our predicted SLQS offer novel insights into the potential involvement of QDH in diverse (patho)biological processes and could represent novel regulatory signals.
ISSN: 0305-1048
DOI: 10.1093/nar/gkv355
Schools: School of Biological Sciences 
School of Physical and Mathematical Sciences 
Rights: © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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