Fig. 8: Proposed model for the tRNA decoding and amino acid sensing by ileS T-box riboswitch in a co-transcriptional manner.

The decoding domain comprised of stem I, II and IIA/B is mainly responsible for recruiting specific tRNAIle, including charged and uncharged tRNAs. When the aminoacylation sensing module was transcribed from RNA polymerase, the AntiS domain folds into preorganized conformation for efficient tRNA NCCA end recognition but the linker region is conformationally dynamic and flexible. If the tRNA is uncharged, the NCCA end will establish stable interactions with AntiS and the linker region stably docked at its preferred conformation. If the tRNA is charged, NCCA end still base pairs with AntiS but the linker region transit frequently from the docked to undocked conformation and in turn leads to the away of stem III from AntiS. Without the stabilization by coaxially stacked stem III and the tertiary contacts contributed by linker region, tRNA NCCA end is easier to dissociate from AntiS. As the SD sequence is transcribed, T-box will probably rearrange the secondary structure to form sequestrator conformation due to the destabilization of AntiS and finally inhibit the translation initiation.