{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:14:42Z","timestamp":1785752082335,"version":"3.56.0"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM106047, GM156496"],"award-info":[{"award-number":["GM106047, GM156496"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-17-059-01-RMC"],"award-info":[{"award-number":["RSG-17-059-01-RMC"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001340","name":"W. W. Smith Charitable Trust","doi-asserted-by":"publisher","award":["C1608"],"award-info":[{"award-number":["C1608"]}],"id":[{"id":"10.13039\/100001340","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["5P30CA056036-17"],"award-info":[{"award-number":["5P30CA056036-17"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>tRNA halves are among the most abundant short non-coding RNAs in the cellular transcriptome. Here we report that in androgen receptor-positive LNCaP prostate cancer cells, the hormone-dependent 5\u2032-tRNA<jats:sup>LysCUU<\/jats:sup> half promoted cell proliferation by facilitating cell cycle progression. Global mRNA profiling upon the 5\u2032-tRNA<jats:sup>LysCUU<\/jats:sup> half depletion revealed that the mRNA of p21, a negative regulator of the cell cycle, is post-transcriptionally destabilized via a 5\u2032-tRNA<jats:sup>LysCUU<\/jats:sup> half-driven mechanism. YBX1, identified as a protein interacting with 5\u2032-tRNA<jats:sup>LysCUU<\/jats:sup> half in the cytosol, was shown to stabilize p21 mRNA. Specific sequences resembling the 5\u2032-tRNA<jats:sup>LysCUU<\/jats:sup> half, located in the 3\u2032-UTR of p21 mRNA and termed LL588, were identified as the binding site for YBX1 and are required for p21 mRNA stability. In vitro binding assays demonstrated that the 5\u2032-tRNA<jats:sup>LysCUU<\/jats:sup> half is capable of displacing YBX1 from LL588. Collectively, our findings suggest that the 5\u2032-tRNA<jats:sup>LysCUU<\/jats:sup> half directly binds to and displaces YBX1 from p21 mRNA, leading to the destabilization of p21 mRNA and the promotion of cell cycle progression in hormone-dependent cancers. Our study illuminates the role of tRNA halves in regulating mRNA stability and suggests that this may be part of broader regulatory networks affecting mRNA levels, orchestrated by various tRNA halves and their interacting proteins.<\/jats:p>","DOI":"10.1371\/journal.pbio.3003194","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T17:32:23Z","timestamp":1749144743000},"page":"e3003194","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["A hormone-dependent tRNA half promotes cell cycle progression via destabilization of p21 mRNA"],"prefix":"10.1371","volume":"23","author":[{"given":"Takuya","family":"Kawamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Shigematsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5232-4742","authenticated-orcid":true,"given":"Yohei","family":"Kirino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"issue":"23","key":"pbio.3003194.ref001","doi-asserted-by":"crossref","first-page":"4297","DOI":"10.1016\/j.febslet.2014.09.001","article-title":"tRNA fragments in human health and disease","volume":"588","author":"P Anderson","year":"2014","journal-title":"FEBS Lett"},{"issue":"17","key":"pbio.3003194.ref002","doi-asserted-by":"crossref","first-page":"9433","DOI":"10.1093\/nar\/gkaa657","article-title":"On the expanding roles of tRNA fragments in modulating cell behavior","volume":"48","author":"R Magee","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pbio.3003194.ref003","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/bbb\/zbae192","article-title":"Angiogenin-catalyzed cleavage within tRNA anticodon-loops identified by cP-RNA-seq","volume":"89","author":"M Shigematsu","year":"2025","journal-title":"Biosci Biotechnol Biochem"},{"issue":"12","key":"pbio.3003194.ref004","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000982","article-title":"Infection-induced 5\u2032-half molecules of tRNAHisGUG activate toll-like receptor 7","volume":"18","author":"K Pawar","year":"2020","journal-title":"PLoS Biol"},{"issue":"29","key":"pbio.3003194.ref005","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1510077112","article-title":"Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers","volume":"112","author":"S Honda","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pbio.3003194.ref006","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/nprot.2016.025","article-title":"Selective amplification and sequencing of cyclic phosphate-containing RNAs by the cP-RNA-seq method","volume":"11","author":"S Honda","year":"2016","journal-title":"Nat Protoc"},{"issue":"5","key":"pbio.3003194.ref007","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41592-023-01813-2","article-title":"A standardized ontology for naming tRNA-derived RNAs based on molecular origin","volume":"20","author":"AD Holmes","year":"2023","journal-title":"Nat Method"},{"issue":"16","key":"pbio.3003194.ref008","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1093\/bioinformatics\/btw194","article-title":"MINTbase: a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments","volume":"32","author":"V Pliatsika","year":"2016","journal-title":"Bioinformatics"},{"issue":"11","key":"pbio.3003194.ref009","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1008469","article-title":"Genome-wide identification of short 2\u2032,3\u2032-cyclic phosphate-containing RNAs and their regulation in aging","volume":"15","author":"M Shigematsu","year":"2019","journal-title":"PLoS Genet"},{"issue":"8","key":"pbio.3003194.ref010","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1080\/15476286.2020.1766861","article-title":"Oxidative stress enhances the expression of 2\u2032,3\u2032-cyclic phosphate-containing RNAs","volume":"17","author":"M Shigematsu","year":"2020","journal-title":"RNA Biol"},{"key":"pbio.3003194.ref011","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.dnarep.2016.04.008","article-title":"Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage","volume":"42","author":"A Karimian","year":"2016","journal-title":"DNA Repair (Amst)"},{"key":"pbio.3003194.ref012","doi-asserted-by":"crossref","first-page":"110073","DOI":"10.1016\/j.cellsig.2021.110073","article-title":"A comprehensive review of the functions of YB-1 in cancer stemness, metastasis and drug resistance","volume":"85","author":"A Alkrekshi","year":"2021","journal-title":"Cell Signal"},{"issue":"4","key":"pbio.3003194.ref013","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.molcel.2011.06.022","article-title":"Angiogenin-induced tRNA fragments inhibit translation initiation","volume":"43","author":"P Ivanov","year":"2011","journal-title":"Mol Cell"},{"issue":"4","key":"pbio.3003194.ref014","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.cell.2015.02.053","article-title":"Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement","volume":"161","author":"H Goodarzi","year":"2015","journal-title":"Cell"},{"issue":"37","key":"pbio.3003194.ref015","doi-asserted-by":"crossref","first-page":"15528","DOI":"10.1073\/pnas.1018949108","article-title":"Differential radial capillary action of ligand assay for high-throughput detection of protein-metabolite interactions","volume":"108","author":"KG Roelofs","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pbio.3003194.ref016","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41576-020-00302-y","article-title":"RNA-binding proteins in human genetic disease","volume":"22","author":"F Gebauer","year":"2021","journal-title":"Nat Rev Genet"},{"issue":"1","key":"pbio.3003194.ref017","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1038\/s41467-022-29790-8","article-title":"TRMT6\/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer","volume":"13","author":"Z Su","year":"2022","journal-title":"Nat Commun"},{"issue":"19","key":"pbio.3003194.ref018","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2319569121","article-title":"The tRNAVal half: a strong endogenous toll-like receptor 7 ligand with a 5\u2019-terminal universal sequence signature","volume":"121","author":"K Pawar","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pbio.3003194.ref019","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1261\/rna.058024.116","article-title":"5\u2019-terminal nucleotide variations in human cytoplasmic tRNAHisGUG and its 5\u2019-halves","volume":"23","author":"M Shigematsu","year":"2017","journal-title":"RNA"},{"issue":"1","key":"pbio.3003194.ref020","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1038\/s41598-017-04429-7","article-title":"Increasing cell density globally enhances the biogenesis of Piwi-interacting RNAs in Bombyx mori germ cells","volume":"7","author":"S Honda","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"pbio.3003194.ref021","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/pro.4218","article-title":"PANTHER: making genome-scale phylogenetics accessible to all","volume":"31","author":"PD Thomas","year":"2022","journal-title":"Protein Sci"},{"issue":"1","key":"pbio.3003194.ref022","doi-asserted-by":"crossref","first-page":"4498","DOI":"10.1038\/s41467-021-24681-w","article-title":"RNase \u03ba promotes robust piRNA production by generating 2\u2032,3\u2032-cyclic phosphate-containing precursors","volume":"12","author":"M Shigematsu","year":"2021","journal-title":"Nat Commun"},{"issue":"8","key":"pbio.3003194.ref023","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nsmb.2347","article-title":"Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis","volume":"19","author":"A Vourekas","year":"2012","journal-title":"Nat Struct Mol Biol"},{"issue":"4","key":"pbio.3003194.ref024","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1261\/rna.037804.112","article-title":"FUS regulates genes coding for RNA-binding proteins in neurons by binding to their highly conserved introns","volume":"19","author":"T Nakaya","year":"2013","journal-title":"RNA"},{"issue":"20","key":"pbio.3003194.ref025","doi-asserted-by":"crossref","first-page":"14296","DOI":"10.1074\/jbc.M511675200","article-title":"Identification of two tRNA thiolation genes required for cell growth at extremely high temperatures","volume":"281","author":"N Shigi","year":"2006","journal-title":"J Biol Chem"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003194","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T17:32:29Z","timestamp":1749144749000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003194"}},"subtitle":[],"editor":[{"given":"Jeff","family":"Coller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,5]]},"references-count":25,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3003194","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,5]]}}}