Alarmone ppGpp directly inhibits tRNA-modifying enzyme MnmE in Bacillus subtilis, affecting biofilm

In Bacillus subtilis, the stress signal ppGpp acts on a tRNA-modification enzyme, which alters translation at AAG codons and controls biofilm matrix production, authors report.

Researchers reported in Science Advances that the alarmone guanosine tetraphosphate (ppGpp) directly inhibits MnmE (TrmE), a conserved GTPase that modifies tRNA. The enzyme is required for methylaminomethyl (mnm) modification of wobble uridine science.org. The work links bacterial stress signaling to codon-specific translational control.

Using high-resolution ribosome profiling in Bacillus subtilis, the authors found that loss of MnmE selectively increases ribosome pausing at AAG codons. It also reprograms translation of a subset of genes, including small open reading frames.

Among them is a previously unrecognized AAG-containing leader peptide that controls expression of the biofilm repressor AbrB. Consistent with this, mnmE mutants produce extracellular matrix constitutively and bypass the biofilm defect of a relA mutant. The authors describe a pathway connecting ppGpp signaling, tRNA modification, codon-specific translation and multicellular development.