{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:25:27Z","timestamp":1791433527183,"version":"4.3.3"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN-148366"],"award-info":[{"award-number":["FDN-148366"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-186015"],"award-info":[{"award-number":["PJT-186015"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-183610"],"award-info":[{"award-number":["PJT-183610"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CIHR PJT-162385"],"award-info":[{"award-number":["CIHR PJT-162385"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Molecular staples or interfacial inhibitors are small molecules that exert their activity through co-association with macromolecules leading to various effects on target functions. Some molecules inhibit target activity, while others generate gain-of-function complexes. We and others have previously identified two structurally distinct classes of molecular staples, pateamine A and rocaglates. These molecules inhibit eukaryotic initiation factor (eIF) 4A, a critical RNA helicase required for translation initiation, by simultaneously interacting with both RNA and protein components. Structural insights from members of these two families indicate that they wedge themselves between RNA bases during engagement. To extend our understanding of rocaglates, we investigated the RNA-binding properties of silvestrol, a natural rocaglate distinguished by the presence of a unique dioxanyloxy ring. Our study demonstrates that silvestrol expands the RNA-binding repertoire\u00a0of rocaglates due to this structural characteristic, providing a rationale for improving synthetic molecular staples targeting eIF4A.<\/jats:p>","DOI":"10.1093\/nar\/gkae824","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T10:40:37Z","timestamp":1727779237000},"page":"12701-12711","source":"Crossref","is-referenced-by-count":14,"title":["Protein\u2013RNA interactions mediated by silvestrol\u2014insight into a unique molecular clamp"],"prefix":"10.1093","volume":"52","author":[{"given":"Sai\u00a0Kiran","family":"Naineni","sequence":"first","affiliation":[{"name":"Department of Biochemistry, McGill University , 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec,","place":["Canada"]},{"name":"Rosalind and Morris Goodman Cancer Research Institute , 1160 Pine Ave W, Montreal, H3A 1A3, Quebec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garvit","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, McGill University , 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec,","place":["Canada"]},{"name":"Department of Pharmacology and Therapeutics, McGill University , 3649 Promenade Sir\u00a0William\u00a0Osler, Montreal H3G\u00a00B1 Quebec ,","place":["Canada"]},{"name":"Centre de Recherche en Biologie Structurale (CRBS), McGill University , 3649 Promenade Sir William Osler, Montreal H3G\u00a00B1 Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkanat","family":"Jiramongkolsiri","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, McGill University , 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec,","place":["Canada"]},{"name":"Rosalind and Morris Goodman Cancer Research Institute , 1160 Pine Ave W, Montreal, H3A 1A3, Quebec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Robert","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, McGill University , 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec,","place":["Canada"]},{"name":"Rosalind and Morris Goodman Cancer Research Institute , 1160 Pine Ave W, Montreal, H3A 1A3, Quebec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Cencic","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, McGill University , 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec,","place":["Canada"]},{"name":"Rosalind and Morris Goodman Cancer Research Institute , 1160 Pine Ave W, Montreal, H3A 1A3, Quebec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2838-4726","authenticated-orcid":false,"given":"Sidong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, McGill University , 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec,","place":["Canada"]},{"name":"Rosalind and Morris Goodman Cancer Research Institute , 1160 Pine Ave W, Montreal, H3A 1A3, Quebec,","place":["Canada"]},{"name":"Department of Human Genetics, McGill University , 3640 University, Room W 315 D, Montreal, H3A 0C7\u00a0 Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-2110","authenticated-orcid":false,"given":"Bhushan","family":"Nagar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, McGill University , 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec,","place":["Canada"]},{"name":"Centre de Recherche en Biologie Structurale (CRBS), McGill University , 3649 Promenade Sir William Osler, Montreal H3G\u00a00B1 Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1963-6466","authenticated-orcid":false,"given":"Jerry","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, McGill University , 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec,","place":["Canada"]},{"name":"Rosalind and Morris Goodman Cancer Research Institute , 1160 Pine Ave W, Montreal, H3A 1A3, Quebec,","place":["Canada"]},{"name":"Department of Oncology, McGill University , 5100 de Maisonneuve Blvd. Montreal\u00a0H4A 3T2\u00a0 Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"key":"2024111111162087200_B1","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1021\/jo040120f","article-title":"Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris","volume":"69","author":"Hwang","year":"2004","journal-title":"J. Org. Chem."},{"key":"2024111111162087200_B2","first-page":"2651","article-title":"Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model","volume":"118","author":"Bordeleau","year":"2008","journal-title":"J. Clin. Invest."},{"key":"2024111111162087200_B3","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.gde.2017.11.001","article-title":"Translation initiation factors and their relevance in cancer","volume":"48","author":"de\u00a0la\u00a0Parra","year":"2018","journal-title":"Curr. Opin. Genet. Dev."},{"key":"2024111111162087200_B4","doi-asserted-by":"crossref","first-page":"e1738","DOI":"10.1002\/wrna.1738","article-title":"Targeting DEAD-box RNA helicases: the emergence of molecular staples","volume":"14","author":"Naineni","year":"2023","journal-title":"Wiley Interdiscip. Rev. 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