{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:43:40Z","timestamp":1785840220317,"version":"3.56.0"},"reference-count":99,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571367"],"award-info":[{"award-number":["31571367"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["31571367"],"award-info":[{"award-number":["31571367"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2019CFB685"],"award-info":[{"award-number":["2019CFB685"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The \u201cRNA World\u201d hypothesis posits a reasonable scenario for the origin of life. A question central to this scenario is: which RNA species may have emerged as the first ribozyme, thereby initiating the earliest stage of life? To date, experimental and computational studies have focused on ribozymes playing a constructive role in RNA synthesis\u2014such as those facilitating template-directed copying or nucleotide synthesis. However, the answer remains unconvincing, primarily because their functional complexity likely demands lengthy sequences, making de novo emergence improbable. Here, we propose an alternative scenario: a destructive ribozyme, which is potentially quite short, may have emerged first. This ribozyme could cleave other RNA molecules to generate building blocks for its own replication. Notably, the dilemma for a destructive ribozyme is that it may degrade molecules of its own type, thus making it difficult to thrive as an RNA species. Using computational modeling, we demonstrate that an exonuclease ribozyme encoded within a circular RNA genome (thus evading self-attack) can spread within an RNA pool and may subsequently give rise to those constructive ribozymes. Our findings offer a new perspective on the initiation of the RNA world, thereby enriching both theoretical and experimental frameworks for understanding the origin of life.<\/jats:p>","DOI":"10.3390\/life16081287","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:15:22Z","timestamp":1785834922000},"page":"1287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exonuclease Ribozyme Encoded in a Circular Genome: On the Initiation of the RNA World"],"prefix":"10.3390","volume":"16","author":[{"given":"Minglun","family":"Liang","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunwu","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Computer Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-7695","authenticated-orcid":false,"given":"Wentao","family":"Ma","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/319618a0","article-title":"The RNA world","volume":"319","author":"Gilbert","year":"1986","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/418214a","article-title":"The antiquity of RNA-based evolution","volume":"418","author":"Joyce","year":"2002","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrg3841","article-title":"The RNA World: Molecular cooperation at the origins of life","volume":"16","author":"Higgs","year":"2015","journal-title":"Nat. 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