Study of RNA-DNA Sequence Differences in Saccharomyces cerevisiae

Abstract: Alteration of transcript sequences and structures, such as those that result from RNA splicing and editing, allows a DNA template to produce two or more RNA transcripts. It was thought that in yeast, RNA editing only occurs in tRNAs. Here, we found that like human cells, 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 rather than the DNA sequences of RDD sites. A screen of yeast mutants showed that RDD formation is affected by mutations in genes regulating R-loops that are part of RNA-DNA hybrids. Deletion of genes that encode the enzymes ribonuclease H, senataxin and topoisomerase I, which resolve RNA-DNA hybrids, leads to an increase in RDD frequency. Our results showed that RDD is a conserved process that diversifies transcriptomes and proteomes.