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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Bibliographic Details
Published in:Nucleic acids research 2012-01, Vol.40 (2), p.e16-e16
Main Authors: Wongsurawat, Thidathip, Jenjaroenpun, Piroon, Kwoh, Chee Keong, Kuznetsov, Vladimir
Format: Article
Language:English
Subjects:
Algorithms
Alternative Splicing
Base Pairing
Databases, Nucleic Acid
DNA - chemistry
Epigenesis, Genetic
Genes
Genome, Human
Humans
Methods Online
Models, Genetic
Mutation
Neoplasms - genetics
Neurodegenerative Diseases - genetics
Recombination, Genetic
RNA - chemistry
Transcription, Genetic
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkr1075