Dissection of context-dependent RNA colocalization landscapes from subcellular spatial transcriptomics data

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Abstract Post-transcriptional RNA processes, including translation, decay, and modification, depend critically on the coordinated spatial organization of RNA molecules. Leveraging densely sampled intracellular RNA distributions from high-resolution spatial transcriptomics (ST), we developed the Subcellular Colocalized RNA Interaction Network (SCRIN) analysis, a computational framework that uses hypergeometric testing to systematically quantify local enrichment of different RNA species. SCRIN robustly reconstructs cell- and tissue-specific RNA colocalization landscapes with high precision. These context-dependent RNA colocalization networks are closely associated with gene functions and biological processes traditionally studied at the protein level. We show that RNA colocalization patterns dynamically reorganize during tissue development and adaptively rewire upon physiological perturbations, representing a widespread and tightly regulated layer of post-transcriptional control. Collectively, our results establish spatiotemporally coordinated RNA interactions as a biologically influential yet underexplored regulatory layer, a significant extension beyond the well-studied protein interaction networks. SCRIN thus opens a new avenue and provides an unprecedented resource for dissecting the functional and mechanistic roles of subcellular transcriptome organization in complex biological processes.
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Dissection of context-dependent RNA colocalization landscapes from subcellular spatial transcriptomics data | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Biological Sciences - Article Dissection of context-dependent RNA colocalization landscapes from subcellular spatial transcriptomics data Xuerui Yang, Xu Chen, Runze Li, Yuanyuan Zeng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7463836/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Post-transcriptional RNA processes, including translation, decay, and modification, depend critically on the coordinated spatial organization of RNA molecules. Leveraging densely sampled intracellular RNA distributions from high-resolution spatial transcriptomics (ST), we developed the Subcellular Colocalized RNA Interaction Network (SCRIN) analysis, a computational framework that uses hypergeometric testing to systematically quantify local enrichment of different RNA species. SCRIN robustly reconstructs cell- and tissue-specific RNA colocalization landscapes with high precision. These context-dependent RNA colocalization networks are closely associated with gene functions and biological processes traditionally studied at the protein level. We show that RNA colocalization patterns dynamically reorganize during tissue development and adaptively rewire upon physiological perturbations, representing a widespread and tightly regulated layer of post-transcriptional control. Collectively, our results establish spatiotemporally coordinated RNA interactions as a biologically influential yet underexplored regulatory layer, a significant extension beyond the well-studied protein interaction networks. SCRIN thus opens a new avenue and provides an unprecedented resource for dissecting the functional and mechanistic roles of subcellular transcriptome organization in complex biological processes. Biological sciences/Biological techniques/Bioinformatics Biological sciences/Computational biology and bioinformatics/Data mining Biological sciences/Genetics/Gene regulation Biological sciences/Molecular biology/Transcriptomics Biological sciences/Systems biology/Regulatory networks Subcellular Colocalized RNA Interaction Network SCRIN spatial transcriptome RNA colocalization landscape RNA interaction post-transcriptional RNA processes Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplTables12.docx Extended Data 2: Supplementary Tables S1-S2 RNACoLocv3.8SupplFig.docx Extended Data 1: Supplementary Figures S1-S5 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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