Dual role of transcription and transcript stability in the regulation of gene expression inEscherichia colicells cultured on glucose at different growth rates

Abstract

Microorganisms extensively reorganize gene expression to adjust growth rate to changes in growth conditions. At the genomic scale, we measured the contribution of both transcription and transcript stability to regulating messenger RNA (mRNA) concentration in Escherichia coli. Transcriptional control was the dominant regulatory process. Between growth rates of 0.10 and 0.63 h−1, there was a generic increase in the bulk mRNA transcription. However, many transcripts became less stable and the median mRNA half-life decreased from 4.2 to 2.8 min. This is the first evidence that mRNA turnover is slower at extremely low-growth rates. The destabilization of many, but not all, transcripts at high-growth rate correlated with transcriptional upregulation of genes encoding the mRNA degradation machinery. We identified five classes of growth-rate regulation ranging from mainly transcriptional to mainly degradational. In general, differential stability within polycistronic messages encoded by operons does not appear to be affected by growth rate. We show here that the substantial reorganization of gene expression involving downregulation of tricarboxylic acid cycle genes and acetyl-CoA synthetase at high-growth rates is controlled mainly by transcript stability. Overall, our results demonstrate that the control of transcript stability has an important role in fine-tuning mRNA concentration during changes in growth rate.

Whole-genome mapping of 5′ RNA ends in bacteria by tagged sequencing: a comprehensive view in Enterococcus faecalis

“…Yet, a major limitation of dRNA-seq is that all transcripts cannot be detected in a single experiment as they are degraded by a 5 ′ -phosphate-dependent exonuclease, and thus information on post-transcriptional events is lost . Global scale analysis of RNA stability has been performed in a few bacterial species, e.g., Bacillus cereus (Kristoffersen et al 2012), Bacillus subtilis (Hambraeus et al 2003), Escherichia coli (Selinger et al 2003;Mohanty and Kushner 2006;Esquerré et al 2013), Mycobaterium tuberculosis (Rustad et al 2013), Lactococcus lactis (Redon et al 2005), and Prochlorococcus (Steglich et al 2010). These stability analyses have highlighted the broad and crucial contribution of RNA stability to gene expression reprogramming when bacteria face stresses, adapt to novel nutrient conditions, or grow at different rates.…”

Genome-wide gene expression and RNA half-life measurements allow predictions of regulation and metabolic behavior in Methanosarcina acetivorans

“…A recent theory was proposed to determine whether change in transcript abundance for a gene between two growth conditions is determined by change in the degradation or transcription rate [7, 8]. The theory defined “control coefficients” that describe the effective change in mRNA level as resulting from degradation or transcription, under the assumption that gene expression is at steady-state (i.e.…”

“…Three regulation regimes are of interest [7–9]: 1) primarily degradationally controlled, ( ρ D ≥1), 2) primarily transcriptionally controlled, ( ρ D ≤0) and 3) mixed degradation and transcription control 0< ρ D <1. The results for all genes can be found in Table 2.…”

“…Regulation of gene expression by change in half-life has recently been demonstrated in L. lactis and E. coli [7–9]. The authors of these papers proposed a method to determine “control coefficients” (which describe whether mRNA abundance is transcriptionally or degradationally controlled) from half-life and expression data.…”

Mycobacterium tuberculosis Metabolism

“…Moreover, recent observations that specific intergenic regions are essential for mycobacterial survival (Zhang et al 2012) or are involved in the emergence of drug resistance (Zhang et al 2013a) hint at a further level of regulation that remains largely unexplored. Metabolic state can also be regulated by other factors; for example, data from E. coli suggest that growth-rate dependent alterations in mRNA stability modulate tricarboxylic cycle activity (Esquerre et al 2013). The possibility, therefore, that the unusually stable transcripts ) characteristic of a slow-growing pathogen have evolved for specific regulatory functions is likely to be tested in future investigations.…”