Posttranscriptional regulation of ribosomal and multiresistance genes by the bacterial leader peptide peTrpL

Ribosome-mediated transcription attenuation in bacteria is an important regulatory mechanism that is controlled by the translation of a short upstream ORF (uORF). Efficient uORF translation causes transcription termination downstream of the uORF. The resulting leader peptide and small attenuator RNA are generally considered nonfunctional. Here, we show that, upon exposure to translation-inhibiting antibiotics, the leader peptide peTrpL (14 aa) of a Sinorhizobium meliloti tryptophan (Trp) biosynthesis operon acts together with its cognate attenuator RNA rnTrpL to destabilize rplUrpmA mRNA which encodes ribosomal proteins. Under these conditions, rnTrpL is produced independently of Trp availability by transcription termination at the attenuator. In addition, the peTrpL peptide has an rnTrpL-independent function in a pathway that is induced by effectors of the TetR-type repressor SmeR. The peTrpL was found to destabilize smeR mRNA, resulting in increased multidrug efflux and multiresistance. The surprising role of peTrpL in antibiotic-triggered posttranscriptional regulation is conserved in other bacteria.