{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:46:49Z","timestamp":1784616409817,"version":"3.55.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-2236996"],"award-info":[{"award-number":["MCB-2236996"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000152","name":"Division of Molecular and Cellular Biosciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000152","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Enteroviruses contain conserved RNA structures at the extreme 5\u2032 end of their genomes that recruit essential proteins 3CD and PCBP2 to promote genome replication. However, the high-resolution structures and mechanisms of these replication-linked RNAs (REPLRs) are limited. Here, we determined the crystal structures of the coxsackievirus B3 and rhinoviruses B14 and C15 REPLRs at 1.54, 2.2 and 2.54 \u00c5 resolution, revealing a highly conserved H-type four-way junction fold with co-axially stacked sA-sD and sB-sC helices that are stabilized by a long-range A\u2022C\u2022U base-triple. Such conserved features observed in the crystal structures also allowed us to predict the models of several other enteroviral REPLRs using homology modeling, which generated models almost identical to the experimentally determined structures. Moreover, our structure-guided binding studies with recombinantly purified full-length human PCBP2 showed that two previously proposed binding sites, the sB-loop and 3\u2032 spacer, reside proximally and bind a single PCBP2. Additionally, the DNA oligos complementary to the 3\u2032 spacer, the high-affinity PCBP2 binding site, abrogated its interactions with enteroviral REPLRs, suggesting the critical roles of this single-stranded region in recruiting PCBP2 for enteroviral genome replication and illuminating the promising prospects of developing therapeutics against enteroviral infections targeting this replication platform.<\/jats:p>","DOI":"10.1093\/nar\/gkae627","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T10:40:57Z","timestamp":1721644857000},"page":"11218-11233","source":"Crossref","is-referenced-by-count":10,"title":["Structural basis for a highly conserved RNA-mediated enteroviral genome replication"],"prefix":"10.1093","volume":"52","author":[{"given":"Naba Krishna","family":"Das","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, Baltimore County , Baltimore , MD\u00a0 21250 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Vogt","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, Baltimore County , Baltimore , MD\u00a0 21250 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, Baltimore County , Baltimore , MD\u00a0 21250 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan Al","family":"Banna","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, Baltimore County , Baltimore , MD\u00a0 21250 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6424-3173","authenticated-orcid":false,"given":"Deepak","family":"Koirala","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, Baltimore County , Baltimore , MD\u00a0 21250 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"2024101410404984800_B1","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1080\/13550280591002531","article-title":"Enteroviruses as agents of emerging infectious diseases","volume":"11","author":"Palacios","year":"2005","journal-title":"J. Neurovirol."},{"key":"2024101410404984800_B2","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.meegid.2012.10.016","article-title":"Picornavirus and enterovirus diversity with associated human diseases","volume":"14","author":"Tapparel","year":"2013","journal-title":"Infect. Genet. 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Gen. Virol."},{"key":"2024101410404984800_B8","doi-asserted-by":"crossref","first-page":"4384","DOI":"10.1128\/jvi.68.7.4384-4391.1994","article-title":"The 5'-untranslated regions of picornavirus RNAs contain independent functional domains essential for RNA replication and translation","volume":"68","author":"Rohll","year":"1994","journal-title":"J. Virol."},{"key":"2024101410404984800_B9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nrm2838","article-title":"The mechanism of eukaryotic translation initiation and principles of its regulation","volume":"11","author":"Jackson","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2024101410404984800_B10","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev-virology-100114-055014","article-title":"A cap-to-tail guide to mRNA translation strategies in virus-infected cells","volume":"3","author":"Jan","year":"2016","journal-title":"Annu. Rev. 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Microbiol."},{"key":"2024101410404984800_B12","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1261\/rna.1031408","article-title":"The cis-acting replication elements define human enterovirus and rhinovirus species","volume":"14","author":"Cordey","year":"2008","journal-title":"RNA"},{"key":"2024101410404984800_B13","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.virusres.2008.07.027","article-title":"Cis-active RNA elements (CREs) and picornavirus RNA replication","volume":"139","author":"Steil","year":"2009","journal-title":"Virus Res."},{"key":"2024101410404984800_B14","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.virol.2009.07.039","article-title":"Functional role of the 5\u2032 terminal cloverleaf in coxsackievirus RNA replication","volume":"393","author":"Sharma","year":"2009","journal-title":"Virology"},{"key":"2024101410404984800_B15","first-page":"623","article-title":"Structure and function of RNA elements present in enteroviral genomes","volume":"63","author":"Dutkiewicz","year":"2016","journal-title":"Acta Biochim. 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Virol."},{"key":"2024101410404984800_B21","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.bbrc.2008.09.156","article-title":"Interaction of poly(rC)-binding protein 2 domains KH1 and KH3 with coxsackievirus RNA","volume":"377","author":"Zell","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2024101410404984800_B22","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1128\/jvi.69.6.3658-3667.1995","article-title":"Interaction between the 5'-terminal cloverleaf and 3AB\/3CDpro of poliovirus is essential for RNA replication","volume":"69","author":"Xiang","year":"1995","journal-title":"J. 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Virol."},{"key":"2024101410404984800_B34","doi-asserted-by":"crossref","first-page":"8850","DOI":"10.1093\/nar\/gkad618","article-title":"Structural basis for cloverleaf RNA-initiated viral genome replication","volume":"51","author":"Gottipati","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"2024101410404984800_B35","doi-asserted-by":"crossref","first-page":"8006","DOI":"10.1093\/nar\/gkaa519","article-title":"Structure of the PCBP2\/stem\u2013loop IV complex underlying translation initiation mediated by the poliovirus type I IRES","volume":"48","author":"Beckham","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2024101410404984800_B36","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1038\/s41467-023-37658-8","article-title":"Crystal structure of a highly conserved enteroviral 5' cloverleaf RNA replication element","volume":"14","author":"Das","year":"2023","journal-title":"Nat. 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