2023-06-01 ミシガン大学
◆ミシガン大学の研究チームは、リボスイッチが自己合成を調節する仕組みを解明しました。リボスイッチが転写を制御する過程を視覚化し、この知見をもとに抗生物質の開発につなげることが期待されています。
<関連情報>
- https://news.umich.edu/high-resolution-images-reveal-workings-of-a-bacterial-rna-riboswitch-a-promising-new-target-for-antibiotics/
- https://www.nature.com/articles/s41594-023-01002-x
リボスイッチとそのリガンドによる細菌RNAポリメラーゼの休止制御の構造的根拠を解明 Structural basis for control of bacterial RNA polymerase pausing by a riboswitch and its ligand
Adrien Chauvier,Jason C. Porta,Indrajit Deb,Emily Ellinger,Katarina Meze,Aaron T. Frank,Melanie D. Ohi & Nils G. Walter
Nature Structural & Molecular Biology Published:01 June 2023
DOI:https://doi.org/10.1038/s41594-023-01002-x
Abstract
Folding of nascent transcripts can be modulated by the RNA polymerase (RNAP) that carries out their transcription, and vice versa. A pause of RNAP during transcription of a preQ1 riboswitch (termed que-PEC) is stabilized by a previously characterized template consensus sequence and the ligand-free conformation of the nascent RNA. Ligand binding to the riboswitch induces RNAP pause release and downstream transcription termination; however, the mechanism by which riboswitch folding modulates pausing is unclear. Here, we report single-particle cryo-electron microscopy reconstructions of que-PEC in ligand-free and ligand-bound states. In the absence of preQ1, the RNA transcript is in an unexpected hyper-translocated state, preventing downstream nucleotide incorporation. Strikingly, on ligand binding, the riboswitch rotates around its helical axis, expanding the surrounding RNAP exit channel and repositioning the transcript for elongation. Our study reveals the tight coupling by which nascent RNA structures and their ligands can functionally regulate the macromolecular transcription machinery.
