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Genome-Wide Profiling of Yeast DNA:RNA Hybrid Prone Sites with DRIP-Chip


RNA processing factors are mutated in human cancers, inherited developmental disorders and neurodegenerative syndromes. Defects in RNA processing have been associated with increased levels of mutations and DNA damage in part via the formation of DNA:RNA hybrids. Although it is likely that specific regions of the genome are more prone to DNA:RNA hybrid formation, a map of hybrid-prone regions is not available. In this study, we describe the genome-wide distribution of DNA:RNA hybrids in both normal and mutant Saccharomyces cerevisiae cells. The resulting profiles contribute to both our understanding of the general properties of hybrid-forming loci and to our knowledge of hybrid-mitigating enzymes. Interestingly, significant DNA:RNA hybrid enrichment was detected at genes associated with antisense transcription. We show that overexpression of RNase H, which degrades the RNA in hybrids, significantly affects the expression of genes associated with antisense transcripts. These findings support a role for DNA:RNA hybrids in regulation of gene expression by antisense transcripts.


Vyšlo v časopise: Genome-Wide Profiling of Yeast DNA:RNA Hybrid Prone Sites with DRIP-Chip. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004288
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004288

Souhrn

RNA processing factors are mutated in human cancers, inherited developmental disorders and neurodegenerative syndromes. Defects in RNA processing have been associated with increased levels of mutations and DNA damage in part via the formation of DNA:RNA hybrids. Although it is likely that specific regions of the genome are more prone to DNA:RNA hybrid formation, a map of hybrid-prone regions is not available. In this study, we describe the genome-wide distribution of DNA:RNA hybrids in both normal and mutant Saccharomyces cerevisiae cells. The resulting profiles contribute to both our understanding of the general properties of hybrid-forming loci and to our knowledge of hybrid-mitigating enzymes. Interestingly, significant DNA:RNA hybrid enrichment was detected at genes associated with antisense transcription. We show that overexpression of RNase H, which degrades the RNA in hybrids, significantly affects the expression of genes associated with antisense transcripts. These findings support a role for DNA:RNA hybrids in regulation of gene expression by antisense transcripts.


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