RNA–DNA sequence differences in Saccharomyces cerevisiae
- Isabel X. Wang1,
- Christopher Grunseich2,
- Youree G. Chung3,
- Hojoong Kwak1,4,
- Girish Ramrattan1,4,
- Zhengwei Zhu1 and
- Vivian G. Cheung1,4,5
- 1Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 2Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 3College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 4Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA;
- 5Departments of Pediatrics and Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA
- Corresponding authors: ixwang{at}umich.edu, vgcheung{at}umich.edu
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.207878.116.
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Freely available online through the Genome Research Open Access option.
- Received April 2, 2016.
- Accepted September 15, 2016.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
