can react in water at neutral pH to form high-energy thioesters<\/a>. These thioesters transfer the activated amino acids to RNA in a process called RNA aminoacylation, preventing them from joining with free-floating amino acids. These findings suggest that thioesters may have provided the energy needed to unite nucleic acids and amino acids for protein biosynthesis\u2014without the need for enzymes\u2014in Earth\u2019s earliest life-forms.<\/p>\nProteins are essential to all life on Earth but, unlike nucleic acids such as DNA and RNA, cannot themselves pass specific sequences to their \u201coffspring.\u201d<\/p>\n
\u201cThis is why life coordinates protein synthesis with another molecule, specifically RNA,\u201d says Matthew W. Powner, lead author of the study (Nature 2025, DOI: 10.1038\/s41586-025-09388-y).<\/p>\n
In modern cells, enzymes called aminoacyl\u2013transfer RNA (tRNA) synthetases attach amino acids to tRNA, activating them and programming the translation of RNA into proteins. But these enzymes themselves are products of the same genetic code\u2014so how were they made in the first place? \u201cBecause you need these proteins to synthesize proteins, it\u2019s a classic chicken-and-the-egg paradox,\u201d Powner says. At life\u2019s origin, these enzymes didn\u2019t exist yet, so the team tried to figure out how amino acids attached to RNA spontaneously in water\u2014the first way life would have had to connect genetic information to functional proteins.<\/p>\n
Developing activated amino acids that react selectively with the 2′,3′-hydroxyl (\u2013OH) groups of the ribose sugar of RNA\u2014without enzymes and with other types of molecules that would be present in a cell or the early Earth at the origins of life\u2014has proven challenging. Past attempts have led to hydrolysis or amino acids reacting with themselves. So the team considered the role that thioesters might play in this process.<\/p>\n
Thioesters are high-energy compounds that are important in many of life\u2019s biochemical processes and, like RNA aminoacylation, have ancient roots in biochemistry that predate the last universal common ancestor of all life on Earth. In the 1990s, Nobel laureate and biochemist Christian de Duve came up with the \u201cthioester world\u201d hypothesis, which posits that, based on their central role in metabolism, life\u2019s first reactions must have been \u201cpowered\u201d by thioesters.<\/p>\n
After synthesizing and purifying nucleotides, nucleic acids, and activated amino acids, the team added thioesters to water at neutral pH at varying temperatures from ambient to freezing. They found that the thioesters were surprisingly stable in water, avoiding unwanted peptide formation between amino acids. In the presence of double-stranded RNA structures, thioesters selectively attached amino acids to the 2′,3′-diol groups of the ribose sugar at the 3′ of the double strand, even amid bulk water and excess amines.<\/p>\n
The team then tested whether RNA could attach a variety of amino acids in water and found that aminoacylation occurred across all four RNA nucleotides on a broad range of amino acids, including charge residues such as arginine and lysine.<\/p>\n
Finally the researchers investigated how these amino acids that were attached to RNA could be used for peptide synthesis under the same plausible prebiotic conditions. They found that when thioesters react with hydrogen sulfide, they form highly reactive thioacids. Those compounds could then be activated to bond with amino acids, even those attached to RNA\u2014switching on peptide synthesis. Ultimately they found that thioesters were selective for aminoacylating RNA, while thioacids enable peptide bond formation, which allows for the stepwise, controlled synthesis of peptides attached to RNA.\u201cA key step missing from prebiotic studies until now has been the use of chemical free energy transfer reactions to overcome the uphill chemistry of assembling polymers in water,\u201d says Charlie Carter, a biochemist and biophysicist at the University of North Carolina School of Medicine who was not involved in this study. \u201cThe simplicity of the chemistry used here strongly suggests that it played a significant role in helping to create conditions for life to emerge,\u201d he adds.<\/p>\n
\n Chemical & Engineering News<\/p>\n
ISSN 0009-2347<\/p>\n
Copyright \u00a9
\n 2025 American Chemical Society<\/p>\n","protected":false},"excerpt":{"rendered":"\u00a0 Researchers at University College London have discovered that activated amino acids and sulfur-containing compounds called thiols\u2014both likely…\n","protected":false},"author":2,"featured_media":114396,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[64,63,50463,81406,64539,17558,1732,81405,128,81407,48846],"class_list":["post-114395","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science","tag-au","tag-australia","tag-origins-of-life","tag-powner","tag-protein-synthesis","tag-reaction-mechanisms","tag-rna","tag-rna-hypothesis","tag-science","tag-thioester","tag-ucl"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/114395","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/comments?post=114395"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/114395\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media\/114396"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media?parent=114395"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/categories?post=114395"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/tags?post=114395"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}