In order to determine whether these observations are a result of changes in mRNA abundance, we calculated GO term enrichment of mRNAs up or down regulated upon glucose or nitrogen starvation and observed sellckchem that down regulated mRNAs are enriched for ribosome and translation related genes, while up regulated mRNAs are enriched for genes related to mitochondrion and meta bolic processes. Therefore, Inhibitors,Modulators,Libraries the GO term enrichment of genes with changes in 3 UTR site occupancy cannot be fully explained by GO term enrichment of up or down regulated mRNAs. Taken together, these data indicate that general nutrient limita tion triggers a remodeling of the post transcriptional regulatory programs of metabolic pathways, while glu cose and nitrogen specific stresses affect additional, dis tinct biological processes.

We further visualized changes in RBP occupancy of 3 UTR crosslinking sites relative to the changes in corre sponding mRNA abundance induced by glucose starvation. Since 3 Inhibitors,Modulators,Libraries UTR crosslinking Inhibitors,Modulators,Libraries sites with decreased RBP occupancy were enriched for mitochondrion related genes, we examined sites on a sub set of these genes encoding mitochondrial membrane components and observed that the crosslinking sites were significantly depleted of RBP occupancy compared to all 3 UTR crosslinking sites, and the mRNAs were significantly up regulated compared to all genes. This observation suggests that 3 UTR crosslinking sites on mRNAs encoding mitochondrial Inhibitors,Modulators,Libraries membrane compo nents are recognized by repressive RBPs, and that upon glucose deprivation, RBP binding is attenuated, resulting in increased mRNA levels.

Mitochondrial aldehyde dehydrogenase ALD4 mRNA is regulated transcriptionally under stress conditions. In our gPAR CLIP data, the ALD4 3 UTR harbors four highly conserved crosslinking sites displaying 2 to 8 fold decreases in RBP occupancy despite a 7 fold increase in ALD4 mRNA levels. These data suggest that post transcriptional regulation of ALD4 Inhibitors,Modulators,Libraries in response to glucose deprivation also occurs through the release of repressive RBP binding at these 3 UTR sites. STM1, which encodes a ribosomal subunit associated pro tein required for optimal translation under nutrient stress, has two 3 UTR crosslinking sites, with one exhibiting 25 fold increased RBP occupancy upon glucose starva tion. STM1 mRNA is con versely down regulated 3 fold, indicating a potential regulatory role for this site involving mRNA stability and or decay.

Interestingly, STM1 mRNA expression HTS is also down regulated upon nitrogen starvation despite no change in RBP occupancy of this site, pointing to non overlapping regulatory mechanisms that contribute to STM1 regulation in glucose and nitrogen starvation conditions. Next we explored changes in RBP occupancy of 3 UTR crosslinking sites relative to changes in corresponding mRNA abundance upon nitrogen starvation.