RT Journal A1 Wang, Isabel X. A1 Grunseich, Christopher A1 Chung, Youree G. A1 Kwak, Hojoong A1 Ramrattan, Girish A1 Zhu, Zhengwei A1 Cheung, Vivian G. T1 RNA–DNA sequence differences in Saccharomyces cerevisiae JF Genome Research JO Genome Research YR 2016 FD November 01 VO 26 IS 11 SP 1544 OP 1554 DO 10.1101/gr.207878.116 UL http://genome.cshlp.org/content/26/11/1544.abstract AB 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. Our results demonstrate that RDD is a conserved process that diversifies transcriptomes and proteomes and provide a mechanistic link between R-loops and RDDs.