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Endogenous small RNAs, such as microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), exhibit structural features supporting their functions and interactions with other biomolecules. Recent advances in RNA foundation models, such as RNA-FM, enable large-scale learning of sequence and structural representations of RNA sequences, offering a powerful framework for studying small-RNA functions. Here, we leverage the RNA-FM alongside interpretable biological features to systematically compare endogenous small RNAs (miRNAs and piRNAs) with synthetic siRNAs. Biological features highlighted type-specific patterns: piRNAs showed significantly higher GC content and melting temperature than miRNAs and siRNAs, suggesting higher stability. Importantly, we mapped RNA-FM embeddings to interpretable features to better understand deep-learning outputs and facilitate effective extraction of functionally relevant information. To support predictive and comparative analyses of small RNAs, we implemented these functionalities in RNAExplorer (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.rnaexplorer.com\">www.rnaexplorer.com<\/jats:ext-link>\n                    ), a web-based application that allows analyzing and visualizing small-RNA features interactively. Together, our integrative analysis provides a framework for understanding small-RNA biology and improving siRNA therapeutic design strategies.\n                  <\/jats:p>","DOI":"10.34133\/csbj.0224","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:12:46Z","timestamp":1788135166000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Leveraging Foundation Models for the Characterization of Small-RNA Properties"],"prefix":"10.34133","volume":"35","author":[{"given":"Shivprasad","family":"Jamdade","sequence":"first","affiliation":[{"name":"School of Cancer and Pharmaceutical Sciences, \rKing\u2019s College London, London SE1 9NQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7505-4754","authenticated-orcid":false,"given":"Coyun","family":"Oh","sequence":"additional","affiliation":[{"name":"School of Cancer and Pharmaceutical Sciences, \rKing\u2019s College London, London SE1 9NQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6600-1255","authenticated-orcid":true,"given":"Heba","family":"Sailem","sequence":"additional","affiliation":[{"name":"School of Cancer and Pharmaceutical Sciences, \rKing\u2019s College London, London SE1 9NQ, UK."},{"name":"King\u2019s AI Institute, \rKing\u2019s College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"21","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1111\/bph.15972","article-title":"Small interfering RNA: Discovery, pharmacology and clinical development\u2014An introductory review","volume":"180","author":"Ranasinghe P","year":"2022","unstructured":"Ranasinghe P, Addison ML, Dear JW, Webb DJ. 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