A Conserved UORF in the MRNA of Species Regulates Operon Expression

Computational methods can be used to identify putative structured noncoding RNAs (ncRNAs) in bacteria, which can then be validated using various biochemical and genetic approaches. In a search for ncRNAs in , we observed a conserved region called the -II motif located upstream of the gene that is also present in other members of this genus. This gene codes for an enzyme involved in the production of branched-chain amino acids (BCAAs). The gene in some bacteria is regulated by members of a ppGpp-sensing riboswitch class, but previous and current data suggest that the -II motif regulates expression by a transcription attenuation mechanism involving protein translation from an upstream open reading frame (uORF or leader peptide). All representatives of this RNA motif carry a start codon positioned in-frame with a nearby stop codon, and the peptides resulting from translation of this uORF are enriched for BCAAs, suggesting that expression of the gene in the host cells is controlled by attenuation. Furthermore, recently discovered RNA motifs also associated with genes in other bacterial species appear to carry distinct uORFs, suggesting that transcription attenuation by uORF translation is a common mechanism for regulating genes.