Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity

R-loop is the structure co-transcriptionally formed between nascent RNA transcript and DNA template, leaving the non-transcribed DNA strand unpaired. This structure can be involved in the hyper-mutation and dsDNA breaks in mammalian immunoglobulin (Ig) genes, oncogenes and neurodegenerative disease...

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Main Authors:	Wongsurawat, Thidathip, Jenjaroenpun, Piroon, Kwoh, Chee Keong, Kuznetsov, Vladimir
Format:	Online
Language:	English
Published:	Oxford University Press 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258121/

id	pubmed-3258121
recordtype	oai_dc
spelling	pubmed-32581212012-01-17 Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity Wongsurawat, Thidathip Jenjaroenpun, Piroon Kwoh, Chee Keong Kuznetsov, Vladimir Methods Online R-loop is the structure co-transcriptionally formed between nascent RNA transcript and DNA template, leaving the non-transcribed DNA strand unpaired. This structure can be involved in the hyper-mutation and dsDNA breaks in mammalian immunoglobulin (Ig) genes, oncogenes and neurodegenerative disease related genes. R-loops have not been studied at the genome scale yet. To identify the R-loops, we developed a computational algorithm and mapped R-loop forming sequences (RLFS) onto 66 803 sequences defined by UCSC as ‘known’ genes. We found that ∼59% of these transcribed sequences contain at least one RLFS. We created R-loopDB (http://rloop.bii.a-star.edu.sg/), the database that collects all RLFS identified within over half of the human genes and links to the UCSC Genome Browser for information integration and visualisation across a variety of bioinformatics sources. We found that many oncogenes and tumour suppressors (e.g. Tp53, BRCA1, BRCA2, Kras and Ptprd) and neurodegenerative diseases related genes (e.g. ATM, Park2, Ptprd and GLDC) could be prone to significant R-loop formation. Our findings suggest that R-loops provide a novel level of RNA–DNA interactome complexity, playing key roles in gene expression controls, mutagenesis, recombination process, chromosomal rearrangement, alternative splicing, DNA-editing and epigenetic modifications. RLFSs could be used as a novel source of prospective therapeutic targets. Oxford University Press 2012-01 2011-11-25 /pmc/articles/PMC3258121/ /pubmed/22121227 http://dx.doi.org/10.1093/nar/gkr1075 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wongsurawat, Thidathip Jenjaroenpun, Piroon Kwoh, Chee Keong Kuznetsov, Vladimir
spellingShingle	Wongsurawat, Thidathip Jenjaroenpun, Piroon Kwoh, Chee Keong Kuznetsov, Vladimir Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity
author_facet	Wongsurawat, Thidathip Jenjaroenpun, Piroon Kwoh, Chee Keong Kuznetsov, Vladimir
author_sort	Wongsurawat, Thidathip
title	Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity
title_short	Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity
title_full	Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity
title_fullStr	Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity
title_full_unstemmed	Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity
title_sort	quantitative model of r-loop forming structures reveals a novel level of rna–dna interactome complexity
description	R-loop is the structure co-transcriptionally formed between nascent RNA transcript and DNA template, leaving the non-transcribed DNA strand unpaired. This structure can be involved in the hyper-mutation and dsDNA breaks in mammalian immunoglobulin (Ig) genes, oncogenes and neurodegenerative disease related genes. R-loops have not been studied at the genome scale yet. To identify the R-loops, we developed a computational algorithm and mapped R-loop forming sequences (RLFS) onto 66 803 sequences defined by UCSC as ‘known’ genes. We found that ∼59% of these transcribed sequences contain at least one RLFS. We created R-loopDB (http://rloop.bii.a-star.edu.sg/), the database that collects all RLFS identified within over half of the human genes and links to the UCSC Genome Browser for information integration and visualisation across a variety of bioinformatics sources. We found that many oncogenes and tumour suppressors (e.g. Tp53, BRCA1, BRCA2, Kras and Ptprd) and neurodegenerative diseases related genes (e.g. ATM, Park2, Ptprd and GLDC) could be prone to significant R-loop formation. Our findings suggest that R-loops provide a novel level of RNA–DNA interactome complexity, playing key roles in gene expression controls, mutagenesis, recombination process, chromosomal rearrangement, alternative splicing, DNA-editing and epigenetic modifications. RLFSs could be used as a novel source of prospective therapeutic targets.
publisher	Oxford University Press
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258121/
_version_	1611499873134182400

Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity

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