Limna - Lausanne Integrative Metabolism Nutrition Alliance


Friday 27th January 2017
10h00 - Department of Physiology - Bugnon 7, Lausanne - Seminar room 6th floor

Single-cell and genome-wide analysis to dissect Long Non-Coding RNAs-mediated gene regulation



University of Geneva

The S. cerevisiae genome codes for a myriad of unstable intergenic and antisense (AS) non-coding transcripts (Neil et al., 2009; Xu et al., 2009). We have previously shown that PHO84 AS RNA stabilization is followed by repression of sense transcription in a process that involves deacetylation of the PHO84 promoter (Camblong et al., 2007). Here we revealed detailed mechanistic aspects of PHO84 antisense RNA mediated regulation at the single cell and single molecule level. In particular, we show that AS transcription acts as an efficient molecular switch to represses sense expression within individual cells (Castelnuovo et al. NSMB 2013). In parallel we analysed with a global approach the generality of antisense-RNA mediated gene repression in S. Cerevisiae. We profiled gene expression in various histone modifying enzymes mutants using high-density tiling arrays to investigate the generality and mechanistic diversity of antisense-mediated gene regulation in the yeast S. cerevisiae. We identified several distinguishing features between functional and non-functional asRNAs, including their sensitivity to early termination by Nrd1/Nab3/Sen1, their extension into the promoter region, or the promoter structure of the corresponding sense gene (Castelnuovo et al. NAR 2014). These findings have important implications on our understanding of AS regulation and antisense-mediated gene repression in eukaryotic cells.

Host : Prof. Ana Marques