Structural basis of amino acid surveillance by higher-order tRNA-mRNA interactions

Shuang Li , Zhaoming Su , Jean Lehmann (1, 2) , Vassiliki Stamatopoulou , Nikoleta Giarimoglou , Frances E. Henderson , Lixin Fan , Grigore D. Pintilie , Kaiming Zhang , Muyuan Chen , Steven J. Ludtke , Yun-Xing Wang , Constantinos Stathopoulos , Wah Chiu , Jinwei Zhang

1 I2BC - Institut de Biologie Intégrative de la Cellule
2 SSFA - Séquence, Structure et Fonction des ARN

Amino acid availability in Gram-positive bacteria is monitored by T-box riboswitches. T-boxes directly bind tRNAs, assess their aminoacylation state, and regulate the transcription or translation of downstream genes to maintain nutritional homeostasis. Here, we report cocrystal and cryo-EM structures of Geobacillus kaustophilus and Bacillus subtilis T-box-tRNA complexes, detailing their multivalent, exquisitely selective interactions. The T-box forms a U-shaped molecular vise that clamps the tRNA, captures its 3' end using an elaborate 'discriminator' structure, and interrogates its aminoacylation state using a steric filter fashioned from a wobble base pair. In the absence of aminoacylation, T-boxes clutch tRNAs and form a continuously stacked central spine, permitting transcriptional readthrough or translation initiation. A modeled aminoacyl disrupts tRNA-T-box stacking, severing the central spine and blocking gene expression. Our data establish a universal mechanism of amino acid sensing on tRNAs and gene regulation by T-box riboswitches and exemplify how higher-order RNA-RNA interactions achieve multivalency and specificity.

Domaines: Sciences du Vivant [q-bio]

Shuang Li, Zhaoming Su, Jean Lehmann, Vassiliki Stamatopoulou, Nikoleta Giarimoglou, et al.. Structural basis of amino acid surveillance by higher-order tRNA-mRNA interactions. Nature Structural and Molecular Biology, 2019, ⟨10.1038/s41594-019-0326-7⟩. ⟨hal-02379385⟩