tRNA-dependent conformational dynamics and folding coordinate translational regulation by a full-length T-box riboswitch
Year: 2025
Type: article
Abstract: T-box riboswitches regulate gene expression by sensing tRNA aminoacylation status, but their dynamic mechanisms remain elusive. Here, we present single-molecule FRET studies of a full-length translational ileS T-box, showing that its decoding domain folds independently, and the initial tRNA anticodon binding promotes proper folding of the discriminator domain. Subsequent uncharged tRNA binding stabilizes the Antisequestrator (AntiS) conformation and GAG linker, resulting in translation initiation. Conversely, charged tRNA binds to a distinct T-box conformation, of which the linker is highly flexible and stem III is away from AntiS, rendering irreversible transition to the Sequestrator conformation if downstream sequences are transcribed, leading to translation inhibition. Collectively, both steps of tRNA binding are in a conformational selection manner, and the GAG linker, especially G96, acts as the main linchpin in tRNA 3΄-termini sensing. An elaborate model is proposed to understand how cotranscriptional folding, stepwise tRNA binding and dynamic conformational transitions coordinate T-box regulation. T-box riboswitches sense tRNA aminoacylation status to regulate gene expression. Here, the authors employ single molecule FRET on a full-length ileS T-box to resolve its structural dynamics, revealing how it distinguishes between tRNA 3’ termini to sense aminoacylation and regulate translation.
Source: Nature Communications
Authors: Xiaolin Niu, Shanshan Cai, Junzheng Wang, Chunlai Chen, Xianyang Fang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4416667967