Amino acids catalyze RNA formation under ambient alkaline conditions

Amino acids catalyze RNA formation under ambient alkaline conditions | 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 Physical Sciences - Article Amino acids catalyze RNA formation under ambient alkaline conditions Dieter Braun, Saroj Rout, Sreekar Wunnava, Matthew Powner, Judit Šponer, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4343389/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract RNA and proteins are the core molecules of life. The sequence of mRNA encodes the protein sequence and proteins orchestrate the replication of nucleic acids. How this synergistic relationship arose remains an unanswered question. Amino acids have not yet provided an evolutionary advantage to nucleic acid synthesis. This relationship has been assumed as a late development during RNA evolution. Here we show that amino acids substantially improve the yield of RNA polymerization from prebiotically plausible ribonucleoside-2',3'-cyclic phosphates. The amino acid catalysis of RNA polymerization was base-selective, increased the compositional oligomer sequence diversity and favoured the formation of natural 3',5' linkages. It was most efficient at pH values close to the pKaH of the amines and correlated with sidechain hydrophobicities, suggesting a general acid-base mechanism akin to ribozyme-catalysed RNA-hydrolysis. This is confirmed by the observed general base-enhanced polymerization of G and U nucleotides. The copolymerization of G/C/A/U with valine resulted in a substantially increased oligomer yield and compositional diversity. The catalytic effect of proteinogenic amino acids on RNA oligomerization suggests the reactivity of amino acids and RNA was united earlier than previously thought, and their association likely predates the genetic code. Biological sciences/Evolution/Chemical origin of life Physical sciences/Chemistry/Chemical origin of life Amino acids RNA ribonucleoside-2' 3'-cyclic phosphates origin of life Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementaryinformation.pdf Methods and Supplementary Figures Cite Share Download PDF Status: Posted 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. 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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-4343389","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Physical Sciences - Article","associatedPublications":[],"authors":[{"id":301130629,"identity":"6d20e3ac-787b-4c73-a2bb-9cbd8670101a","order_by":0,"name":"Dieter 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