{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:08:28Z","timestamp":1790766508165,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"14","funder":[{"name":"US National Institutes of Health Intramural Research Program"},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["ES103247"],"award-info":[{"award-number":["ES103247"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["ES103326"],"award-info":[{"award-number":["ES103326"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1ZIAES103340"],"award-info":[{"award-number":["1ZIAES103340"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Coronaviruses generate double-stranded (ds) RNA intermediates during viral replication that can activate host immune sensors. To evade activation of the host pattern recognition receptor MDA5, coronaviruses employ Nsp15, which is a\u00a0uridine-specific endoribonuclease. Nsp15 is proposed to associate with the coronavirus replication-transcription complex within double-membrane vesicles to cleave these dsRNA intermediates. How Nsp15 recognizes and processes dsRNA is poorly understood because previous structural studies of Nsp15 have been limited to small single-stranded (ss) RNA substrates. Here we present cryo-EM structures of SARS-CoV-2 Nsp15 bound to a 52nt dsRNA. We observed that the Nsp15 hexamer forms a platform for engaging dsRNA across multiple protomers. The structures, along with site-directed mutagenesis and RNA cleavage assays revealed critical insight into dsRNA recognition and processing. To process dsRNA Nsp15 utilizes a base-flipping mechanism to properly orient the uridine within the active site for cleavage. Our findings show that Nsp15 is a distinctive endoribonuclease that can cleave both ss- and dsRNA effectively.<\/jats:p>","DOI":"10.1093\/nar\/gkac589","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T09:16:44Z","timestamp":1657271804000},"page":"8290-8301","source":"Crossref","is-referenced-by-count":52,"title":["Flipped over U: structural basis for dsRNA cleavage by the SARS-CoV-2 endoribonuclease"],"prefix":"10.1093","volume":"50","author":[{"given":"Meredith N","family":"Frazier","sequence":"first","affiliation":[{"name":"Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , 111 T. W. Alexander Drive , Research Triangle Park, NC \u00a027709,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha M","family":"Wilson","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , 111 T. W. Alexander Drive , Research Triangle Park, NC \u00a027709,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juno M","family":"Krahn","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , 111 T. W. Alexander Drive , Research Triangle Park, NC \u00a027709,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin John","family":"Butay","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , 111 T. W. Alexander Drive , Research Triangle Park, NC \u00a027709,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas\u00a0B","family":"Dillard","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , 111 T. W. Alexander Drive , Research Triangle Park, NC \u00a027709,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario\u00a0J","family":"Borgnia","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , 111 T. W. Alexander Drive , Research Triangle Park, NC \u00a027709,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2106-3102","authenticated-orcid":false,"given":"Robin\u00a0E","family":"Stanley","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , 111 T. W. Alexander Drive , Research Triangle Park, NC \u00a027709,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"2022081123573324900_B1","doi-asserted-by":"crossref","first-page":"12910","DOI":"10.1074\/jbc.REV120.013930","article-title":"The molecular virology of coronaviruses","volume":"295","author":"Hartenian","year":"2020","journal-title":"J. Biol. Chem."},{"key":"2022081123573324900_B2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: implications for SARS-CoV-2","volume":"19","author":"V\u2019Kovski","year":"2021","journal-title":"Nat. Rev. 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