Complementary iTRAQ proteomics and RNA-seq transcriptomics reveal multiple levels of regulation in response to nitrogen starvation in Synechocystis sp. PCC 6803.

Sequential adaptation to environmental stress needs complex regulation at different cellular levels in cyanobacteria. To uncover the regulatory mechanism in response to nitrogen starvation, we investigated the genome-wide correlation between protein abundance and gene expression in a model cyanobacterium Synechocystis sp. PCC 6803 using complementary quantitative iTRAQ proteomics and RNA-seq transcriptomics. Consistent with the cell growth inhibition, proteomic analysis indicated phase-dependent down-regulation of proteins related to nitrogen metabolism, ribosome complexes, glycolysis pathway and tricarboxylic acid (TCA) cycles by nitrogen starvation. Transcriptomic analysis also showed that genes related to "Photosynthesis", "Protein synthesis" and "Energy metabolism" were significantly down-regulated by nitrogen starvation. Interestingly, the concordance between protein abundances and their corresponding mRNAs exhibited a functional categories-dependent pattern, with some categories, such as "Protein synthesis" and "Energy metabolism", having a relatively high correlation, while others even with numerous discordant changes in protein-mRNA pairs, indicated divergent regulation of transcriptional and post-transcriptional processes. In particular, an increased abundance of proteins related to "Photosynthesis" upon nitrogen starvation was found to be reversely correlated with the down-regulation of their corresponding mRNAs. In addition, two metabolic modules highly correlated with nitrogen starvation were identified by a co-expression network analysis, and were found to contain mostly photosynthetic proteins and hypothetical proteins, respectively. We further confirmed the involvement of the photosynthetic genes in nitrogen starvation tolerance by constructing and analyzing the psbV gene deletion mutant.