title: RNA-DNA sequence differences in Saccharomyces cerevisiae.
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. Our results demonstrate that RDD is a conserved process that diversifies transcriptomes and proteomes and provide a mechanistic link between R-loops and RDDs.
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Isabel X
authors.initials: IX
authors.lastname: Wang
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Grunseich
authors.affiliation: College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Youree G
authors.initials: YG
authors.lastname: Chung
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.|Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.
authors.forename: Hojoong
authors.initials: H
authors.lastname: Kwak
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.|Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.
authors.forename: Girish
authors.initials: G
authors.lastname: Ramrattan
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.|Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.|Departments of Pediatrics and Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Vivian G
authors.initials: VG
authors.lastname: Cheung
mesh_terms: D020137:Base Pair Mismatch; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics*; D000073658:Loss of Function Mutation; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D016914:Ribonuclease H / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D004271:DNA, Fungal; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D016914:Ribonuclease H; D004264:DNA Topoisomerases, Type I