Abstract
Bacterial adaptation requires large-scale regulation of gene expression. We have performed a genome-wide analysis of the Csr system, which regulates many important cellular functions. The Csr system is involved in post-transcriptional regulation, but a role in transcriptional regulation has also been suggested. Two proteins, an RNA-binding protein CsrA and an atypical signaling protein CsrD, participate in the Csr system. Genome-wide transcript stabilities and levels were compared in wildtype E. coli (MG1655) and isogenic mutant strains deficient in CsrA or CsrD activity demonstrating for the first time that CsrA and CsrD are global negative and positive regulators of transcription, respectively. The role of CsrA in transcription regulation may be indirect due to the 4.6-fold increase in csrD mRNA concentration in the CsrA deficient strain. Transcriptional action of CsrA and CsrD on a few genes was validated by transcriptional fusions. In addition to an effect on transcription, CsrA stabilizes thousands of mRNAs. This is the first demonstration that CsrA is a global positive regulator of mRNA stability. For one hundred genes, we predict that direct control of mRNA stability by CsrA might contribute to metabolic adaptation by regulating expression of genes involved in carbon metabolism and transport independently of transcriptional regulation.
Highlights
Binding protein, and CsrD, a putative signaling protein, and two regulatory sRNAs, CsrB and CsrC11
We show that in our experimental condition CsrA and CsrD are both involved in massive transcriptional regulation whereas genome-wide regulation of mRNA stability is only dependent on CsrA
Considering this result, we have compared the transcriptomic responses in the MG1655(csrA51) and MG1655(Δ csrD) strains. 77% (1878/2444) of differentially expressed mRNAs in MG1655(csrA51) were differentially expressed in Δ csrD and for most of them (1653/1878) the regulation was in opposite directions: most of the up-regulated mRNAs in MG1655(csrA51) were down-regulated in the MG1655(Δ csrD) strain. These results show that mutations of CsrA and CsrD induce strong but opposite global regulation of mRNA levels and that the transcriptomic response observed in the MG1655(csrA51) strain could be at least partially mediated by CsrD
Summary
Binding protein, and CsrD, a putative signaling protein, and two regulatory sRNAs, CsrB and CsrC11. Besides its role in mRNA stability, the Csr system is involved in post-translational regulation through the CsrA-dependent activation of enzyme activity[18]. How the Csr system combines transcriptional and post-transcriptional regulation at the genome-wide scale to control major physiological functions is not yet determined. We show that in our experimental condition CsrA and CsrD are both involved in massive transcriptional regulation whereas genome-wide regulation of mRNA stability is only dependent on CsrA. We discuss these results in terms of direct and indirect effects, and show how the direct control of mRNA stability by CsrA contributes to metabolic adaptation
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