Dataset Information

Selective RNA Processing and Stabilization are Multi-Layer and Stoichiometric Regulators of Gene Expression in Escherichia coli.

ABSTRACT: Selective RNA processing and stabilization (SRPS) facilitates the differential expression of multiple genes in polycistronic operons. However, how the coordinated actions of SRPS-related enzymes affect stoichiometric regulation remains unclear. In the present study, the first genome-wide targetome analysis is reported of these enzymes in Escherichia coli, at a single-nucleotide resolution. A strictly linear relationship is observed between the RNA pyrophosphohydrolase processing ratio and scores assigned to the first three nucleotides of the primary transcript. Stem-loops associated with PNPase targetomes exhibit a folding free energy that is negatively correlated with the termination ratio of PNPase at the 3' end. More than one-tenth of the RNase E processing sites in the 5'-untranslated regions（UTR） form different stem-loops that affect ribosome-binding and translation efficiency. The effectiveness of the SRPS elements is validated using a dual-fluorescence reporter system. The findings highlight a multi-layer and quantitative regulatory method for optimizing the stoichiometric expression of genes in bacteria and promoting the application of SRPS in synthetic biology.

SUBMITTER: Liu D

PROVIDER: S-EPMC10667835 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Selective RNA Processing and Stabilization are Multi-Layer and Stoichiometric Regulators of Gene Expression in Escherichia coli.

Liu Daixi D Lv Haibo H Wang Yafei Y Chen Jinyu J Li Dexin D Huang Ranran R

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231016 33

Selective RNA processing and stabilization (SRPS) facilitates the differential expression of multiple genes in polycistronic operons. However, how the coordinated actions of SRPS-related enzymes affect stoichiometric regulation remains unclear. In the present study, the first genome-wide targetome analysis is reported of these enzymes in Escherichia coli, at a single-nucleotide resolution. A strictly linear relationship is observed between the RNA pyrophosphohydrolase processing ratio and scores ...[more]

PMID: 37845007

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Project description:We analyzed the within-household evolution of two household-associated Escherichia coli strains from pandemic clonal group ST131-H30, using isolates recovered from five individuals within two families, each of which had a distinct strain. Family 1's strain was represented by a urine isolate from the index patient (older sister) with recurrent cystitis and a blood isolate from her younger sister with fatal urosepsis. Family 2's strain was represented by a urine isolate from the index patient (father) with pyelonephritis and renal abscesses, blood and kidney drainage isolates from the daughter with emphysematous pyelonephritis, and urine and fecal isolates from the mother with cystitis. Collectively, the several variants of each family's strain had accumulated a total of 8 (family 1) and 39 (family 2) point mutations; no two isolates were identical. Of the 47 total mutations, 36 resulted in amino acid changes or truncation of coded proteins. Fourteen such mutations (39%) targeted genes encoding transcriptional regulators, and 9 (25%) involved DNA-binding transcription factors (TFs), which significantly exceeded the relative contribution of TF genes to the isolates' genomes (∼6%). At least one-half of the transcriptional regulator mutations were inactivating, based on phenotypic and/or transcriptional analysis. In particular, inactivating mutations in the global regulator LrhA (repressor of type 1 fimbriae and flagella) occurred in the blood isolates from both households and increased the virulence of E. coli strains in a murine sepsis model. The results indicate that E. coli undergoes adaptive evolution between and/or within hosts, generating subpopulations with distinctive phenotypes and virulence potential.IMPORTANCE The clonal evolution of bacterial strains associated with interhost transmission is poorly understood. We characterized the genome sequences of clonal descendants of two Escherichia coli strains, recovered at different time points from multiple individuals within two households who had different types of urinary tract infection. We found evidence that the E. coli strains underwent extensive mutational diversification between and within these individuals, driven disproportionately by inactivation of transcriptional regulators. In urosepsis isolates, the mutations observed in the global regulator LrhA increased bacterial virulence in a murine sepsis model. Our findings help in understanding the adaptive dynamics and strategies of E. coli during short-term natural evolution.

Dataset Information

Selective RNA Processing and Stabilization are Multi-Layer and Stoichiometric Regulators of Gene Expression in Escherichia coli.

Publications

Selective RNA Processing and Stabilization are Multi-Layer and Stoichiometric Regulators of Gene Expression in Escherichia coli.

Similar Datasets

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