Unravelling Mechanisms Controlling Gene Expression Noise in Saccharomyces cerevisiae during Rapid Adaptive Responses

The Nrd1-Nab3-Sen1 (NNS) complex terminates transcription of approximately 12,000 RNAs in Saccharomyces cerevisiae. During the stress response, the NNS complex changes its occupancy to reprogram gene expression.

Some of the transcripts that are only targeted by the NNS complex during the adaptive response are specifically upregulated during glucose starvation. PIC2, which encodes for a mitochondrial copper importer, is one of these NNS stress-specific targets.

Whereas lack of PIC2 expression leads to defective mitochondrial respiration in yeast and humans, overexpression of copper transporters makes standard copper levels toxic for cells.

Accordingly, we hypothesise that PIC2 expression is tightly regulated by the NNS complex, which suppresses transcriptional noise during glucose depletion.

We will compare the phenotype of strains encoding for wild-type and deleted PIC2 NNS RNA-binding sites in varying concentrations of glucose and copper, and determine whether the variability of PIC2 expression during glucose deprivation is higher when NNS regulation is impeded.

Our results could validate the NNS complex as one of the first stress-specific suppressors of stochastic expression, outline a methodology to test this role in similar NNS targets, provide a synthetic biology tool to repress gene expression in yeast and shed light on how transcriptional noise elicits human disease.