Downloaded from genome.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press RNA-DNA Sequence Differences in Saccharomyces cerevisiae I. X. Wang1*, C. Grunseich2, Y. G. Chung3, H. Kwak1,4, G. Ramrattan1,4, Z. Zhu1, V. G. Cheung1,4,5* 1Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA 2Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. 3College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA 4Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA 5Departments of Pediatrics and Genetics, University of Michigan, Ann Arbor, MI 48109, USA *
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[email protected]. Running title: RNA-DNA sequence differences in budding yeast Keywords: RNA editing; RNA-DNA sequence differences; R-loops Downloaded from genome.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press ABSTRACT Alterations of RNA sequences and structures, such as those from editing and alternative splicing, result in two or more RNA transcripts from a DNA template. It was thought that in yeast, RNA editing only occurs in tRNAs. Here, we found that Saccharomyces cerevisiae have all 12 types of RNA-DNA sequence differences (RDDs) in the mRNA. We showed these sequence differences are propagated to proteins, as we identified peptides encoded by the RNA sequences in addition to those by the DNA sequences at RDD sites. RDDs are significantly enriched at regions with R-loops. A screen of yeast mutants showed that RDD formation is affected by mutations in genes regulating R-loops. Loss-of-function mutations in ribonuclease H, senataxin and topoisomerase I that resolve RNA-DNA hybrids lead to increases in RDD frequency.