The T-box leader is a highly conserved RNA regulatory element that is involved in regulation of various genes involved in amino acid metabolism in Gram-positive bacteria, mostly in the Firmicutes phylum [19932103]. T-box elements initially identified in the regulatory leader regions of aminoacyl-tRNA synthetase genes and some amino acid biosynthetic genes in Bacillus subtilis and related bacteria control gene expression via a unique transcription antitermination mechanism [8045882, 8289305]. T-box serves as a riboswitch that binds directly to a specific uncharged tRNA and thus measures the amino acid availability in the cell. more

The most T-box leaders can fold to form two alternative hairpin structures, an intrinsic transcriptional terminator or a competing transcription antiterminator. The formation of the terminator hairpin results in a premature termination of transcription. The proper pairing of an appropriate uncharged tRNA with the T-box leader RNA promotes the stabilization of the alternative antiterminator structure, preventing the formation of the terminator. Some of T-box leaders in certain bacteria control gene expression of the level of translation, when the leader RNAs do not have a terminator helix, and instead include a structure with the ability to sequester the Shine-Dalgarno sequence for the downstream gene [19258532]. Binding of uncharged tRNA stabilizes an alternative structure analogous to the antiterminator, that releases the Shine-Dalgarno sequence for translation initiation. The sequence signature of T-box leaders is very specific and thus they can be readily identified in the complete genomes. Multiple alignment and secondary RNA structure prediction for T-box leaders identified in bacterial genomes allow defining their amino acid specificity through the analysis of the specifier codon [19258532, 18359782, 18625071]. The specifier codon is a determinant recognized by the tRNA anticodon, which is positioned at a discrete location in the specifier loop within stem I. in the genomic searches, T-box leaders with specifier codons corresponding to 19 amino acids have been identified [19258532, 18359782, 18625071]. Thus, the T-box-regulated genes and operons can be attributed to one out of 19 amino acid-specific T-box regulons. Analysis of candidate T-box sites resulted in new functional annotations, in particular, several new types of candidate amino acid transporters were identified [18359782, 18625071].