{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:48:44Z","timestamp":1790279324638,"version":"4.1.0"},"reference-count":98,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"Wellcome Trust\/DBT India Alliance","doi-asserted-by":"crossref","award":["IA\/I\/17\/2\/503313"],"award-info":[{"award-number":["IA\/I\/17\/2\/503313"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"crossref"}]},{"award":["IA\/I\/17\/2\/503313"],"award-info":[{"award-number":["IA\/I\/17\/2\/503313"]}],"id":[{"id":"https:\/\/ror.org\/04reqzt68","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Picornaviruses employ internal ribosome entry sites (IRESs) in their genomic RNA to hijack the host\u2019s translational machinery. The picornavirus, encephalomyocarditis virus, employs a type 2 IRES present in its 5\u2019 untranslated region (5\u2019UTR) and requires 43S ribosomal preinitiation complex (PIC), the central domain of eukaryotic initiation factor (eIF) 4G, eIF4A, and an essential ITAF (IRES trans-acting factor)-polypyrimidine tract binding protein 1 (PTB1) to form 48S PIC. In this study, we have used cryo-electron microscopy (cryo-EM) to determine the structure of encephalomyocarditis virus (EMCV) IRES-bound mammalian 48S PIC in a scanning-arrested closed state at the start codon. The EMCV IRES domains contact initiator tRNA (tRNA\n                    <jats:sub>i<\/jats:sub>\n                    ) and 40S head at the inter-subunit interface, which reveals an altogether unique mechanism used by viruses to capture host translational machinery for its protein synthesis. The tRNA\n                    <jats:sub>i<\/jats:sub>\n                    is held away from the 40S body in contrast to canonical cap-dependent translation while the domain I apical region of EMCV IRES mimics 28S rRNA of 60S to interact with 40S ribosomal head proteins uS13 and uS19. The structural analysis accounts for numerous previously reported biochemical studies on type 2 IRES and shows how type 2 IRES interacts with 43S PIC to form 48S PIC. This study provides mechanistic insights for understanding EMCV IRES-mediated translation initiation, which could be extrapolated to other IRESs sharing similar motifs and factor requirements, including type 1 viral IRESs.\n                  <\/jats:p>","DOI":"10.7554\/elife.107788","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T14:30:16Z","timestamp":1755873016000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.107788","source":"Crossref","is-referenced-by-count":0,"title":["Structural insights into the recruitment of viral type 2 IRES to ribosomal preinitiation complex for protein synthesis"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3138-4033","authenticated-orcid":true,"given":"Deepakash","family":"Das","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dese585","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Developmental Biology and Genetics, Indian Institute of Science","place":["Bangalore, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4735-2380","authenticated-orcid":true,"given":"Tanweer","family":"Hussain","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dese585","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Developmental Biology and Genetics, Indian Institute of Science","place":["Bangalore, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108476","type":"journal-article","article-title":"The halastavi \u00e1rva virus intergenic region ires promotes translation by the simplest possible initiation mechanism","volume":"33","author":"Abaeva","year":"2020","journal-title":"Cell Reports"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"9294","DOI":"10.1093\/nar\/gkad569","type":"journal-article","article-title":"The structure and mechanism of action of a distinct class of dicistrovirus intergenic region IRESs","volume":"51","author":"Abaeva","year":"2023","journal-title":"Nucleic Acids Research"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00358-23","type":"journal-article","article-title":"Advances and breakthroughs in IRES-directed translation and replication of picornaviruses","volume":"14","author":"Abdullah","year":"2023","journal-title":"mBio"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","type":"journal-article","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019102226","type":"journal-article","article-title":"The Israeli acute paralysis virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs","volume":"38","author":"Acosta-Reyes","year":"2019","journal-title":"The EMBO Journal"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1107\/S2059798318006551","type":"journal-article","article-title":"Real-space refinement in PHENIX for cryo-EM and crystallography","volume":"74","author":"Afonine","year":"2018","journal-title":"Acta Crystallographica. 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