{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T20:08:08Z","timestamp":1768680488657,"version":"3.49.0"},"reference-count":61,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan society for the promotion of science (JSPS)","doi-asserted-by":"publisher","award":["23H02741"],"award-info":[{"award-number":["23H02741"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transfer RNA-derived small RNAs (tDRs) are increasingly being recognized as versatile regulators, yet their physiological landscape remains poorly charted. We analyzed tDR expression in seven adult mouse tissues to explore tissue-specific tDR enrichment using a tDR-optimized library preparation methodology. We catalogued 26,901 unique nuclear tDRs (ntDRs) and 5114 mitochondrial tDRs (mtDRs). Clustering analysis segregated the tissues, with the spleen and lungs forming a distinct immune cluster. Tissue-versus-all and pairwise differential analysis showed the spleen harboring unique ntDRs and mtDRs. Tissue-enriched tDRs arose from specific isoacceptor and isodecoder tRNAs, independent of mature tRNA abundance, suggesting selective biogenesis rather than bulk turnover. G-quadruplex prediction revealed a pronounced enrichment of potentially quadruplex-forming ntDRs in the kidneys, heart, and spleen, predominantly derived from i-tRFs and tRF3 fragments, suggesting structure-dependent functions in immune regulation. We also benchmarked our library strategy against the PANDORA-seq method. Despite comparable or lower sequencing depth, our method detected ~3\u201310-fold more unique ntDRs and we observed a clearer representation of tRF-3 fragments and greater isotype diversity. Our tissue atlas and improved tDR sequencing method reveal extensive tissue-specific heterogeneity in tDR biogenesis, sequencing, and structure, providing a framework for understanding the context-dependent regulatory roles of tDRs.<\/jats:p>","DOI":"10.3390\/ijms26188772","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"8772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimized tDR Sequencing Reveals Diversity and Heterogeneity in tRNA-Derived Fragment Landscapes in Mouse Tissues"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8180-7196","authenticated-orcid":false,"given":"Daisuke","family":"Ando","sequence":"first","affiliation":[{"name":"Department of Neurosurgical Engineering, Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8575, Japan"},{"name":"Division of Development and Discovery of Interventional Therapy, Tohoku University Hospital, Sendai 980-8574, Japan"},{"name":"Department of Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"},{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4511-6360","authenticated-orcid":false,"given":"Sherif","family":"Rashad","sequence":"additional","affiliation":[{"name":"Department of Neurosurgical Engineering, Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8575, Japan"},{"name":"Department of Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9282-6499","authenticated-orcid":false,"given":"Kuniyasu","family":"Niizuma","sequence":"additional","affiliation":[{"name":"Department of Neurosurgical Engineering, Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8575, Japan"},{"name":"Division of Development and Discovery of Interventional Therapy, Tohoku University Hospital, Sendai 980-8574, Japan"},{"name":"Department of Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"},{"name":"Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3953","DOI":"10.1016\/j.molcel.2023.09.016","article-title":"tRNA renovatio: Rebirth through fragmentation","volume":"83","author":"Kuhle","year":"2023","journal-title":"Mol. 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