Genome-wide screening reveals metabolic regulation of stop-codon readthrough by cyclic AMP.

ABSTRACT: Translational fidelity is critical for microbial fitness, survival and stress responses. Much remains unknown about the genetic and environmental control of translational fidelity and its single-cell heterogeneity. In this study, we used a high-throughput fluorescence-based assay to screen a knock-out library of Escherichia coli and identified over 20 genes critical for stop-codon readthrough. Most of these identified genes were not previously known to affect translational fidelity. Intriguingly, we show that several genes controlling metabolism, including cyaA and crp, enhance stop-codon readthrough. CyaA catalyzes the synthesis of cyclic adenosine monophosphate (cAMP). Combining RNA sequencing, metabolomics and biochemical analyses, we show that deleting cyaA impairs amino acid catabolis

SUBMITTER: Lyu Z 

PROVIDER: S-EPMC10570021 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature