Diverse Environmental Stresses Elicit Distinct Responses at the Level of Pre-mRNA Processing in Yeast.. Saccharomyces cerevisiae

Gene expression in Eukaryotic cells is profoundly shaped by the post-transcriptional processing of mRNAs, including the splicing of introns in the nucleus and both nuclear and cytoplasmic degradation pathways. Here we report the use of a splicing isoform specific microarray platform to investigate the effects of a host of diverse stress conditions on both splicing pre-mRNA fate. Interestingly, We find that diverse stresses cause distinct patterns of changes at the level of pre- mRNA processing. The responses we observed are most dramatic for the RPGs and can be categorized into three major classes. The first is characterized by accumulation of RPG pre-mRNA and is seen in multiple types of amino acid starvation regimes; the magnitude of splicing inhibition correlates with the severity of the stress. The second class is characterized by a rapid decrease in both pre- and mature RPG mRNA and is seen in many stresses that inactivate the TORC1 kinase complex. These decreases depend on nuclear turn-over of the intron-containing pre-RNAs. The third class is characterized by a decrease in RPG pre-mRNA with only a modest reduction in the mature species; this response is observed in hyperosmotic and cation-toxic stresses. We show that casein kinase 2 (CK2) makes important contributions to the changes in pre-mRNA processing, particularly for the first two classes of stress responses. In total, our data suggest that complex post-transcriptional programs cooperate to fine-tune expression of intron-containing transcripts in budding yeast. Overall design: Splicing-specific microarrays were used to assay the changes to splicing caused by a wide variety of environmental stresses and nutrient conditions.