TY - JOUR TI - Pausing guides RNA folding to populate transiently stable RNA structures for riboswitch-based transcription regulation AU - Steinert, Hannah AU - Sochor, Florian AU - Wacker, Anna AU - Buck, Janina AU - Helmling, Christina AU - Hiller, Fabian AU - Keyhani, Sara AU - Noeske, Jonas AU - Grimm, Steffen AU - Rudolph, Martin M AU - Keller, Heiko AU - Mooney, Rachel Anne AU - Landick, Robert AU - Suess, Beatrix AU - Fürtig, Boris AU - Wöhnert, Jens AU - Schwalbe, Harald A2 - Kay, Lewis E VL - 6 PY - 2017 DA - 2017/05/25 SP - e21297 C1 - eLife 2017;6:e21297 DO - 10.7554/eLife.21297 UR - https://doi.org/10.7554/eLife.21297 AB - In bacteria, the regulation of gene expression by cis-acting transcriptional riboswitches located in the 5'-untranslated regions of messenger RNA requires the temporal synchronization of RNA synthesis and ligand binding-dependent conformational refolding. Ligand binding to the aptamer domain of the riboswitch induces premature termination of the mRNA synthesis of ligand-associated genes due to the coupled formation of 3'-structural elements acting as terminators. To date, there has been no high resolution structural description of the concerted process of synthesis and ligand-induced restructuring of the regulatory RNA element. Here, we show that for the guanine-sensing xpt-pbuX riboswitch from Bacillus subtilis, the conformation of the full-length transcripts is static: it exclusively populates the functional off-state but cannot switch to the on-state, regardless of the presence or absence of ligand. We show that only the combined matching of transcription rates and ligand binding enables transcription intermediates to undergo ligand-dependent conformational refolding. KW - RNA KW - riboswitches KW - meta-stable structures KW - folding KW - transcription KW - kinetics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -