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Here, we present Graph-based RNA Substructure-Aware Subcellular localization Prediction (GRASP), a unified graph neural network framework for predicting RNA subcellular localization using a heterogeneous graph representation that is RNA substructure-aware. GRASP presents each RNA as a multi-scale graph comprising nucleotide nodes and secondary-structure-derived substructure nodes, connected by relational edges, enabling joint modeling of base-level interactions and regional structural context. The model further incorporates multi-label dependency learning to capture co-localization patterns across cellular compartments within a unified framework. Across multiple benchmark datasets and RNA types, GRASP consistently outperforms state-of-the-art sequence-based and structure-informed methods, achieving substantial improvements in accuracy, F1-score, and area under the curve (AUC) while maintaining strong scalability to long transcripts. In addition, the graph-based representation provides biologically interpretable insights into structural determinants of RNA localization. The source code and data are available at https:\/\/github.com\/ABILiLab\/GRASP, and the web server is accessible at https:\/\/grasp.biotools.bio.<\/jats:p>","DOI":"10.1093\/bib\/bbag325","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:42:43Z","timestamp":1779968563000},"source":"Crossref","is-referenced-by-count":0,"title":["Graph-based RNA structural representation reveals determinants of subcellular localization"],"prefix":"10.1093","volume":"27","author":[{"given":"Yi","family":"Hao","sequence":"first","affiliation":[{"name":"College of Information Engineering, Northwest A&F University , Yangling, Shaanxi 712100 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heyun","family":"Sun","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide University , Adelaide, South Australia 5005 ,","place":["Australia"]},{"name":"School of Information Technology, Deakin University , Burwood, Victoria 3125 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixu","family":"Ran","sequence":"additional","affiliation":[{"name":"College of Information Engineering, Northwest A&F University , Yangling, Shaanxi 712100 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Information Engineering, Northwest A&F University , Yangling, Shaanxi 712100 ,","place":["China"]},{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide University , Adelaide, South Australia 5005 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Information Technology, Deakin University , Burwood, Victoria 3125 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