Antisense expression increases gene expression variability and locus interdependency

Molecular Systems Biology

Zhenyu Xu¹  Wu Wei¹  Julien Gagneur¹  Sandra Clauder-Münster¹  Miłosz Smolik¹  Wolfgang Huber¹ 

[1] Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany

关键词: antisense regulation;    gene expression;    non‐coding RNA;    transcriptome;   

DOI  :  10.1038/msb.2011.1

来源: Wiley

【 摘 要 】

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.

Synopsis

The function of non-coding antisense RNAs in yeast remains to be fully understood. Steinmetz and colleagues provide evidence for a general regulatory effect of antisense expression on sense genes and for a role in spreading regulatory signals between neighboring genes.

Antisense expression, the RNA expression on the opposite strand of coding genes, is widespread but its general role has remained elusive. By expression profiling yeast in different environments and genetic backgrounds, the authors observed that genes with antisense are more frequently switched-off and show higher expression variability. This effect is the outcome of repression that specifically acts on low levels of sense expression—a model that is experimentally validated for the SUR7 locus. Furthermore, antisense expression is shown to connect the regulation of neighbouring loci in a setting where the bidirectional promoter of a gene initiates expression antisense to an upstream gene. Together, these findings underline the regulatory potential of the downstream region of genes as promoters of antisense transcripts and indicate antisense expression as a regulatory mechanism to enhance switch-like expression for stress–response and condition-specific genes.

【 授权许可】

CC BY-NC-SA   
Copyright © 2011 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.