title: Antisense expression increases gene expression variability and locus interdependency.
abstract: Genome-wide transcription profiling has revealed extensive expression of non-coding RNAs antisense to genes, yet their functions, if any, remain to be understood. In this study, we perform a systematic analysis of sense-antisense expression in response to genetic and environmental changes in yeast. We find that antisense expression is associated with genes of larger expression variability. This is characterized by more 'switching off' at low levels of expression for genes with antisense compared to genes without, yet similar expression at maximal induction. By disrupting antisense transcription, we demonstrate that antisense expression confers an on-off switch on gene regulation for the SUR7 gene. Consistent with this, genes that must respond in a switch-like manner, such as stress-response and environment-specific genes, are enriched for antisense expression. In addition, our data provide evidence that antisense expression initiated from bidirectional promoters enables the spreading of regulatory signals from one locus to neighbouring genes. These results indicate a general regulatory effect of antisense expression on sense genes and emphasize the importance of antisense-initiating regions downstream of genes in models of gene regulation.
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xu
authors.forename: Wu
authors.initials: W
authors.lastname: Wei
authors.forename: Julien
authors.initials: J
authors.lastname: Gagneur
authors.forename: Sandra
authors.initials: S
authors.lastname: Clauder-Münster
authors.forename: Miłosz
authors.initials: M
authors.lastname: Smolik
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Huber
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
mesh_terms: D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D056426:Genetic Loci / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013312:Stress, Physiological; D014158:Transcription, Genetic
chemical_list: D008565:Membrane Proteins; D016372:RNA, Antisense; D012331:RNA, Fungal; D022661:RNA, Untranslated; C502213:SUR7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins