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Standalone RNA-seq from Direct regulation of a tRNA modification enzyme by ppGpp links stress signaling to translational control and biofilm development

ABSTRACT: tRNA modifications influence decoding efficiency and translational fidelity, yet how they are integrated into bacterial signaling networks remains poorly understood. Here, we identify a direct connection between stress signaling and codon-specific translational regulation. We show that the alarmone ppGpp directly inhibits MnmE (TrmE), a conserved GTPase required for wobble uridine modification. High-resolution ribosome profiling in Bacillus subtilis revealed that loss of MnmE selectively increases ribosome pausing at AAG codons and reprograms translation of a subset of genes, including small open reading frames. Among these is a previously unrecognized AAG-containing leader peptide that controls expression of the biofilm repressor AbrB. Consistent with this mechanism, mnmE mutants exhibit constitutive extracellular matrix production and bypass the biofilm defect of a relA mutant. Together, these findings establish a pathway linking ppGpp signaling, tRNA modification, codon-specific translation, and multicellular development.

ORGANISM(S): Bacillus subtilis subsp. subtilis NCIB 3610 = ATCC 6051 = DSM 10

PROVIDER: GSE313102 | GEO | 2026/09/25

REPOSITORIES: GEO

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RIBO-seq and matched RNA-seq _ Direct regulation of a tRNA modification enzyme by ppGpp links stress signaling to translational control and biofilm development

Project description:tRNA modifications influence decoding efficiency and translational fidelity, yet how they are integrated into bacterial signaling networks remains poorly understood. Here, we identify a direct connection between stress signaling and codon-specific translational regulation. We show that the alarmone ppGpp directly inhibits MnmE (TrmE), a conserved GTPase required for wobble uridine modification. High-resolution ribosome profiling in Bacillus subtilis revealed that loss of MnmE selectively increases ribosome pausing at AAG codons and reprograms translation of a subset of genes, including small open reading frames. Among these is a previously unrecognized AAG-containing leader peptide that controls expression of the biofilm repressor AbrB. Consistent with this mechanism, mnmE mutants exhibit constitutive extracellular matrix production and bypass the biofilm defect of a relA mutant. Together, these findings establish a pathway linking ppGpp signaling, tRNA modification, codon-specific translation, and multicellular development.

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