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T-box leader
Usually found in gram-positive bacteria, the T box leader sequence is an RNA element that controls gene expression through the regulation of translation by binding directly to a specific tRNA and sensing its aminoacylation state.[1] This interaction controls expression of downstream aminoacyl-tRNA synthetase genes, amino acid biosynthesis, and uptake-related genes in a negative feedback loop.[1][2] The uncharged tRNA acts as the effector for transcription antitermination of genes in the T-box leader family.[3][4][5] The anticodon of a specific tRNA base pairs to a specifier sequence within the T-box motif, and the NCCA acceptor tail of the tRNA base pairs to a conserved bulge in the T-box antiterminator hairpin.[6] tRNA-mediated attenuationAlthough the exact mechanism of T box leader is still unclear and currently being studied, it has recently been recognized as a member of an expanding group of RNAs that are phylogenetically conserved across many gram-positive bacteria.[2] They are structurally complex and able to directly sense physiological signals which results in the control of downstream gene expression.[2] This controlling of gene expression is accomplished by transcriptional attenuation—a general transcriptional regulation strategy that senses when an alteration in the rate of transcription is necessary and initiating alteration at a particular site (sometimes preceding one or more genes of an operon).[7] The operons that encode aminoacyl-tRNA synthetases, regulated by tRNA-mediated transcriptional attenuation, contain a leader region that specifies a transcript segment that can fold and eventually form a complex set of structures.[7] Two of the most crucial segments to attenuation function as both the terminator and the antiterminator in different regulatory situations.[7]   Leader structureIn terms of structure, the T box RNA is highly conserved—especially in the stem I distal region.[1] The stem I region forms an arched conformation, with the apex containing a complex loop-loop interaction between the conserved adenine-guanine bulge and distal loop.[1] This loop-loop structure is similar to that seen in the ribosome exit site, suggesting that it is highly conserved among tRNA recognition sites.[1] The apex of the stem I region recognizes two critical positions on the tRNA: the anticodon and D/T-loops.[8] Extensive intermolecular interactions occur at this site.[8] If the length or orientation of these two recognition points is altered or mismatched, the T box riboswitch and tRNA complex is disrupted, and proper functioning of transcriptional regulation cannot occur.[8][9] Riboswitch functionThe riboswitch functions by directly sensing a physiological signal.[10] Next, a specific uncharged tRNA binds to a riboswitch element in the transcript, and a structural change occurs in the transcript that promotes expression of the downstream coding sequence.[2][10] The specifier sequence is the first recognition sequence in the leader.[7] It is complementary to the anticodon of the tRNA that is a substrate of the tRNA synthetase under regulation.[7] The second tRNA binding sequence, the T box sequence, is complementary to the nucleotide preceding the acceptor end of the tRNA.[7] The T box is found in the side bulge of the antiterminator.[7] Method of regulationThe most common model system used to study T-box leader is in the gram-positive bacterium Bacillus subtilis.[10] In terms of what is currently understood about the regulatory role of T box function, it appears that when the uncharged tRNA is abundant, it binds to the specifier and the T box sequence of an appropriate leader RNA, stabilizing the antiterminator and, in turn, preventing terminator formation.[7] Without terminator formation, transcription will proceed.[7] If, however, the tRNA is charged, its acceptor end will be blocked by an amino acid and thus, cannot pair with the T box.[7] The terminator will then form, thereby terminating transcription.[7] External links
References
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