Systematic functional and mechanistic analysis of gene regulation by antisense transcription in Saccharomyces cerevisiae

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Cellular protein homeostasis ensures optimal levels of every protein at the location of its function within the organism. Protein homeostasis is governed by a series of regulatory circuits at multiple levels of the cellular machinery, from transcription to proteome turnover. Recent studies have revealed the existence of pervasive non-coding transcription in eukaryotes, whereby a large fraction of genes overlap with non-coding antisense transcripts. Several single-gene studies have demonstrated that these antisense transcripts play significant roles in regulating expression of the sense gene. The scope of this project is to globally characterize the functions and mechanisms of antisense-mediated regulation, via targeted disruptions of antisense transcription, using yeast as a model organism. In a collaboration between a genome biology and bioinformatics oriented group and a cell biology oriented group, we will apply a systematic high-throughput approach to study the impact of antisense transcription on protein expression levels and cell-specific expression, using a comprehensive collection of sense-antisense pairs across the genome. The aim of the project is to decipher the phenotypic impact, molecular mechanisms and functional rationale of antisense transcriptional control by means of both global and focused mechanistic studies, using high content live cell microscopy, high-throughput genetic analysis, and phenotypic profiling.