Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study
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...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2015
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| Online Access: | https://hdl.handle.net/10356/81102 http://hdl.handle.net/10220/39095 |
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| author | Lim, Kah Wai Jenjaroenpun, Piroon Low, Zhen Jie Khong, Zi Jian Ng, Yi Siang Kuznetsov, Vladimir Andreevich Phan, Anh Tuan |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Lim, Kah Wai Jenjaroenpun, Piroon Low, Zhen Jie Khong, Zi Jian Ng, Yi Siang Kuznetsov, Vladimir Andreevich Phan, Anh Tuan |
| author_sort | Lim, Kah Wai |
| collection | NTU |
| description | 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. |
| first_indexed | 2025-02-19T03:48:18Z |
| format | Journal Article |
| id | ntu-10356/81102 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:48:18Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/811022023-02-28T16:58:24Z Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study Lim, Kah Wai Jenjaroenpun, Piroon Low, Zhen Jie Khong, Zi Jian Ng, Yi Siang Kuznetsov, Vladimir Andreevich Phan, Anh Tuan School of Biological Sciences School of Physical and Mathematical Sciences Physics & Applied Physics Biological Sciences 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. Published version 2015-12-16T07:43:07Z 2019-12-06T14:21:27Z 2015-12-16T07:43:07Z 2019-12-06T14:21:27Z 2015 Journal Article 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. 0305-1048 https://hdl.handle.net/10356/81102 http://hdl.handle.net/10220/39095 10.1093/nar/gkv355 25958397 en Nucleic Acids Research © 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 (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 17 p. application/pdf |
| spellingShingle | Physics & Applied Physics Biological Sciences Lim, Kah Wai Jenjaroenpun, Piroon Low, Zhen Jie Khong, Zi Jian Ng, Yi Siang Kuznetsov, Vladimir Andreevich Phan, Anh Tuan Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study |
| title | Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study |
| title_full | Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study |
| title_fullStr | Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study |
| title_full_unstemmed | Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study |
| title_short | Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study |
| title_sort | duplex stem loop containing quadruplex motifs in the human genome a combined genomic and structural study |
| topic | Physics & Applied Physics Biological Sciences |
| url | https://hdl.handle.net/10356/81102 http://hdl.handle.net/10220/39095 |
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