{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T05:00:56Z","timestamp":1775192456359,"version":"3.50.1"},"reference-count":82,"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":[{"name":"Academy of Medical Sciences Springboard","award":["SBF007\\100026"],"award-info":[{"award-number":["SBF007\\100026"]}]},{"name":"Royal Society Research","award":["RGS\\R1\\221075"],"award-info":[{"award-number":["RGS\\R1\\221075"]}]},{"name":"Patrick Johnston Research Fellowship"},{"name":"Royal Society Research","award":["RGS\\R2\\222149"],"award-info":[{"award-number":["RGS\\R2\\222149"]}]},{"DOI":"10.13039\/501100000770","name":"University of Manchester","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000770","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brainwaves Northern Ireland"},{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of Turkey","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013684","name":"Christie Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013684","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000873","name":"Queen's University Belfast","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000873","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>Ribosome quality control (RQC) resolves collided ribosomes, thus preventing their cytotoxic effects. The chemotherapeutic agent 5-Fluorouracil (5FU) is best known for its misincorporation into DNA and inhibition of thymidylate synthase. However, while a major determinant of 5FU\u2019s anticancer activity is its misincorporation into RNAs, the mechanisms by which cancer cells overcome the RNA-dependent 5FU toxicity remain ill-defined. Here, we report a role for RQC in mitigating the cytotoxic effects of 5FU. We show that 5FU treatment results in rapid induction of the mTOR signalling pathway, enhanced rate of mRNA translation initiation, and increased ribosome collisions. Consistently, a defective RQC exacerbates the 5FU-induced cell death, which is mitigated by blocking mTOR pathway or mRNA translation initiation. Furthermore, 5FU treatment enhances the expression of the key RQC factors ZNF598 and GIGYF2 via an mTOR-dependent post-translational mechanism. This adaptation likely mitigates the cytotoxic consequences of increased ribosome collisions upon 5FU treatment.<\/jats:p>","DOI":"10.1093\/nar\/gkae849","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T15:44:32Z","timestamp":1726587872000},"page":"12534-12548","source":"Crossref","is-referenced-by-count":12,"title":["Ribosome Quality Control mitigates the cytotoxicity of ribosome collisions induced by 5-Fluorouracil"],"prefix":"10.1093","volume":"52","author":[{"given":"Susanta","family":"Chatterjee","sequence":"first","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Parisa","family":"Naeli","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Okan","family":"Onar","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]},{"name":"Department of Biology, Faculty of Science, Ankara University , Ankara,\u00a0","place":["Turkey"]}]},{"given":"Nicole","family":"Simms","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester \u00a0M13 9NT,","place":["UK"]}]},{"given":"Aitor","family":"Garzia","sequence":"additional","affiliation":[{"name":"Laboratory of RNA Molecular Biology, The Rockefeller University , 1230 York Avenue , New\u00a0York , NY\u00a0 10065 ,","place":["USA"]}]},{"given":"Angela","family":"Hackett","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Kelsey","family":"Coyle","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Patric","family":"Harris\u00a0Snell","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Tom","family":"McGirr","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Tanvi Nitin","family":"Sawant","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Kexin","family":"Dang","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester \u00a0M13 9NT,","place":["UK"]}]},{"given":"Zornitsa\u00a0Vasileva","family":"Stoichkova","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester \u00a0M13 9NT,","place":["UK"]}]},{"given":"Yumna","family":"Azam","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Mark\u00a0P","family":"Saunders","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester \u00a0M13 9NT,","place":["UK"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6666-4868","authenticated-orcid":false,"given":"Michael","family":"Braun","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester \u00a0M13 9NT,","place":["UK"]}]},{"given":"Tommy","family":"Alain","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa , Ottawa , ON K1H 8L1 ,","place":["Canada"]}]},{"given":"Thomas","family":"Tuschl","sequence":"additional","affiliation":[{"name":"Laboratory of RNA Molecular Biology, The Rockefeller University , 1230 York Avenue , New\u00a0York , NY\u00a0 10065 ,","place":["USA"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-4773","authenticated-orcid":false,"given":"Simon\u00a0S","family":"McDade","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Daniel\u00a0B","family":"Longley","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"Christos\u00a0G","family":"Gkogkas","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Foundation for Research and Technology-Hellas, University Campus , 45110 \u00a0 Ioannina ,","place":["Greece"]}]},{"given":"Colin","family":"Adrain","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]},{"given":"John\u00a0R P","family":"Knight","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester \u00a0M13 9NT,","place":["UK"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5129-7081","authenticated-orcid":false,"given":"Seyed Mehdi","family":"Jafarnejad","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast \u00a0BT7\u00a09AE,","place":["UK"]}]}],"member":"286","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"key":"2024111111240857700_B1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-fluorouracil: mechanisms of action and clinical strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. Rev. 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