Regulatory landscapes and structural choreography of transcription initiation in spirochetes

Regulatory landscapes and structural choreography of transcription initiation in spirochetes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Regulatory landscapes and structural choreography of transcription initiation in spirochetes Georgiy Belogurov, Vilma Trapp, Tingting Wang, Tarek Hilal, Janne Mäkinen, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8863462/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Spirochaetota is a deeply rooted bacterial phylum of evolutionary and medical importance. We show that the spirochetal RNA polymerase (RNAP) has a diminished ability to melt promoters compared to its Escherichia coli counterpart. This deficiency is compensated by CarD and is not linked to the phylum's natural resistance to the antibiotic rifampicin. CryoEM analysis revealed that the spirochetal RNAP disengages the -35 element during promoter unwinding, which contrasts with other bacterial RNAPs that release this element later during the initial transcription. Our research also details the unusually tight, non-sequence-specific binding of the spirochetal RNAP holoenzyme to DNA, which may be linked to the highly extended structure of the spirochetal nucleoid. We support these observations with a structural analysis of the dimeric holoenzyme non-specifically bound to DNA. Our results highlight the functional diversity of bacterial transcription systems and lay the foundation for understanding transcription regulation in pathogenic spirochetes. Biological sciences/Molecular biology/Transcription/Transcriptional regulatory elements Biological sciences/Microbiology/Bacteria/Bacterial transcription Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Trappetalsupplementarydatafile.zip Supplementary Data File SupplementaryInformationncv2.pdf Supplementary Information SupplementaryMovie1.mp4 Supplementary Movie 1 SupplementaryMovie2.mp4 Supplementary Movie 2 PDBvalidationreports.zip PDB validation reports Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8863462","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":598131397,"identity":"a35f8653-0a40-430d-bc73-a900d6d9c48b","order_by":0,"name":"Georgiy 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