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A mechanism for ligand gated strand displacement in ZTP riboswitch transcription regulation

View ORCID ProfileEric J. Strobel, View ORCID ProfileLuyi Cheng, View ORCID ProfileKatherine E. Berman, View ORCID ProfilePaul D. Carlson, View ORCID ProfileJulius B. Lucks
doi: https://doi.org/10.1101/521930
Eric J. Strobel
1Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA
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  • For correspondence: eric.strobel@northwestern.edu jblucks@northwestern.edu
Luyi Cheng
2Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208, USA
4Center for Synthetic Biology, Northwestern University, Evanston, IL, 20208
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Katherine E. Berman
2Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208, USA
4Center for Synthetic Biology, Northwestern University, Evanston, IL, 20208
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Paul D. Carlson
3Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, 14853, USA
4Center for Synthetic Biology, Northwestern University, Evanston, IL, 20208
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Julius B. Lucks
1Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA
4Center for Synthetic Biology, Northwestern University, Evanston, IL, 20208
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  • For correspondence: eric.strobel@northwestern.edu jblucks@northwestern.edu
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Abstract

Cotranscriptional RNA folding forms structural intermediates that can be critically important for RNA biogenesis. This is especially true for transcriptional riboswitches that must undergo ligand-dependent structural changes during transcription to regulate the synthesis of downstream genes. Here, we systematically map the folding states traversed by the Clostridium beijerinckii pfl riboswitch as it controls transcription termination in response to the purine biosynthetic intermediate ZMP. We find that after rearrangement of a non-native hairpin to form the ZTP aptamer, cotranscriptional ZMP binding stabilizes two structural elements that lead to antitermination by tuning the efficiency of terminator hairpin nucleation and strand displacement. We also uncover biases within natural ZTP riboswitch sequences that could avoid misfolded intermediates that disrupt function. Our findings establish a mechanism for ZTP riboswitch control of transcription that has similarities to the mechanisms of diverse riboswitches and provide evidence of selective pressure at the level of cotranscriptional RNA folding pathways.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 16, 2019.
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A mechanism for ligand gated strand displacement in ZTP riboswitch transcription regulation
Eric J. Strobel, Luyi Cheng, Katherine E. Berman, Paul D. Carlson, Julius B. Lucks
bioRxiv 521930; doi: https://doi.org/10.1101/521930
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A mechanism for ligand gated strand displacement in ZTP riboswitch transcription regulation
Eric J. Strobel, Luyi Cheng, Katherine E. Berman, Paul D. Carlson, Julius B. Lucks
bioRxiv 521930; doi: https://doi.org/10.1101/521930

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