Pervasive formation of double-stranded RNAs by overlapping sense/antisense transcripts in budding yeast mitosis and meiosis

Abstract

Previous RNA profiling studies revealed coexpression of overlapping sense/antisense (s/a) transcripts in pro- and eukaryotic organisms. Functional analyses in yeast have shown that certain s/a mRNA/mRNA and mRNA/lncRNA pairs form stable double-stranded RNAs (dsRNAs) that affect transcript stability. Little is known, however, about the genome-wide prevalence of dsRNA formation and its potential functional implications during growth and development in diploid budding yeast. To address this question, we monitored dsRNAs in a Saccharomyces cerevisiae strain expressing the ribonuclease DCR1 and the RNA-binding protein AGO1 from Naumovozyma castellii. We identify dsRNAs at 347 s/a loci that express partially or completely overlapping transcripts during mitosis, meiosis, or both stages of the diploid life cycle. We associate dsRNAs with s/a loci previously thought to be exclusively regulated by antisense interference, and others that encode antisense RNAs, which down-regulate sense mRNA-encoded protein levels. To facilitate hypothesis building, we developed the sense/antisense double-stranded RNA (SensR) expression viewer. Users are able to retrieve different graphical displays of dsRNA and RNA expression data using genome coordinates and systematic or standard names for mRNAs and different types of stable or cryptic long noncoding RNAs (lncRNAs). Our data are a useful resource for improving yeast genome annotation and for work on RNA-based regulatory mechanisms controlling transcript and protein levels. The data are also interesting from an evolutionary perspective, since natural antisense transcripts that form stable dsRNAs have been detected in many species from bacteria to humans. The SensR viewer is freely accessible at https://sensr.genouest.org.