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New insights into how residence time of RNA polymerase and refolding kinetics must be fine-tuned for the regulation of transcription

June 2017. It has been increasingly recognized that the folding of RNA is intimately linked to transcription kinetics, which are directly dependent on transcriptional pausing. The synthesis of the RNA is not performed at a constant speed. Instead, slow conformational changes, from a more competent to a less competent transcription state, lead to a variation of the transcription speed of the elongation complex. This elemental pausing occurs frequently, but typically lasts only for 1–6 s on average. Pausing can also facilitate the folding of certain RNA structures and allow a stabilizing interaction between the nascent RNA and the transcription machinery.

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. A team of scientists from Goethe University Frankfurt, the University of Wisconsin–Madison and the Technical University Darmstadt now 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. The scientists show that only the combined matching of transcription rates and ligand binding enables transcription intermediates to undergo ligand-dependent conformational refolding.
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Harald Schwalbe
Institute of Organic Chemistry and Chemical Biology
Goethe University Frankfurt
Frankfurt am Main, Germany

Steinert H, Sochor F, Wacker A, Buck J, Helmling C, Hiller F, Keyhani S, Noeske J, Grimm SK, Rudolph MM, Keller H, Mooney RA, Landick R, Suess B, Fürtig B*, Wöhnert J*, Schwalbe H* (2017) Pausing guides RNA folding to populate transiently stable RNA structures for riboswitch-based transcription regulation. eLife 6: e21297. http://dx.doi.org/10.7554/eLife.21297


Cluster of Excellence Macromolecular Complexes, Frankfurt am Main, Germany