{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:37:54Z","timestamp":1785893874231,"version":"3.56.0"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["602130"],"award-info":[{"award-number":["602130"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Epileptogenesis involves widespread molecular remodeling, including transcriptional and post\u2010transcriptional changes that reshape neuronal networks. While microRNAs have been extensively studied in this context, the contribution of transfer RNA\u2010derived small RNAs (tsRNAs) remains largely unexplored. Understanding how tsRNAs engage in Argonaute 2 (Ago2)\u2010mediated regulation during epileptogenesis could uncover new layers of post\u2010transcriptional control relevant to seizure development and progression. Recent studies increasingly recognize transfer RNA\u2010derived small RNAs or tsRNAs, especially those bound to Argonaute 2 (Ago2), as functional regulators of gene expression. Here, we analyzed Ago2\u2010immunoprecipitated small RNA\u2010Seq data along with matching transcriptomic and proteomic data across seven defined timepoints in a rat model of epilepsy that was induced using perforant pathway stimulation (PPS). The analysis showed dynamic shifts in Ago\u20102 bound tsRNA expression, with early and intermediate stages showing upregulation of shorter tsRNA fragments, whereas Day of First Seizure (DOFS) and chronic timepoints showed a shift toward 5\u2032 tiRNAs, including highly upregulated GlyGCC\u2010derived fragments. Cluster analysis using Weighted Gene Co\u2010Expression Network Analysis (WGCNA) identified modules specific to the DOFS timepoint where tsRNAs clustered together with genes enriched in pathways including neuronal metabolism, mitochondrial function, and synaptic stability. Target prediction analysis using RNAhybrid at DOFS predicted targets in 3\u2032 UTR, 5\u2032 UTR, and CDS regions showing an association with glycolysis, protein localization, and vesicle trafficking. Subsequent gene\u2010disease association analysis further associated the predicted targets with neurodegenerative conditions including but not limited to Alzheimer's disease, intellectual disability, and epilepsy. This study highlights that tsRNAs potentially play a temporal dynamic regulatory role in epileptogenesis with an evident shift in tsRNA accumulation at DOFS suggesting a potential rewiring of post\u2010transcriptional control at the completion of epileptogenesis. This work also highlights a first integrative approach of tsRNA downstream effects on the transcriptome and proteome in epilepsy and suggests innovative tsRNA\u2010driven mechanisms relevant to disease progression.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70317-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70317","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T10:49:26Z","timestamp":1765795766000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Temporal Dynamics of\n                    <scp>tsRNA<\/scp>\n                    Regulation Mark an Abrupt Transition After Epileptogenesis"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-551X","authenticated-orcid":false,"given":"Saad","family":"Zaheer","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Medical Physics and RCSI Centre for Systems Medicine RCSI University of Medicine and Health Sciences  Dublin Ireland"},{"name":"FutureNeuro Research Ireland Centre RCSI University of Medicine and Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharada","family":"Baindoor","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Medical Physics and RCSI Centre for Systems Medicine RCSI University of Medicine and Health Sciences  Dublin Ireland"},{"name":"FutureNeuro Research Ireland Centre RCSI University of Medicine and Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6005-1307","authenticated-orcid":false,"given":"Niamh M. C.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Medical Physics and RCSI Centre for Systems Medicine RCSI University of Medicine and Health Sciences  Dublin Ireland"},{"name":"FutureNeuro Research Ireland Centre RCSI University of Medicine and Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Siebenbrodt","sequence":"additional","affiliation":[{"name":"Goethe\u2010University Frankfurt, Epilepsy Center Frankfurt Rhine\u2010Main, Department of Neurology University Medical Center  Frankfurt Germany"},{"name":"Center for Personalized Translational Epilepsy Research (CePTER) Goethe\u2010University Frankfurt  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Bauer","sequence":"additional","affiliation":[{"name":"Goethe\u2010University Frankfurt, Epilepsy Center Frankfurt Rhine\u2010Main, Department of Neurology University Medical Center  Frankfurt Germany"},{"name":"Center for Personalized Translational Epilepsy Research (CePTER) Goethe\u2010University Frankfurt  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Rosenow","sequence":"additional","affiliation":[{"name":"Goethe\u2010University Frankfurt, Epilepsy Center Frankfurt Rhine\u2010Main, Department of Neurology University Medical Center  Frankfurt Germany"},{"name":"Center for Personalized Translational Epilepsy Research (CePTER) Goethe\u2010University Frankfurt  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens S.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Center for Experimental Bioinformatics University of Southern Denmark  Odense M Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten T.","family":"Ven\u00f8","sequence":"additional","affiliation":[{"name":"Omiics ApS  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen","family":"Kjems","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nanoscience Center, Dept. of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Henshall","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Medical Physics and RCSI Centre for Systems Medicine RCSI University of Medicine and Health Sciences  Dublin Ireland"},{"name":"FutureNeuro Research Ireland Centre RCSI University of Medicine and Health Sciences  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen H. 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