Systematic discovery of subcellular RNA patterns in the gut epithelium

系统性地发现肠道上皮细胞亚细胞RNA模式

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作者:Minkyoung Lee ,Ilhan E Acar ,Davide Eletto ,Srivathsan Adivarahan ,Farah Mhamedi ,Kristina Handler ,Jihyun Lee ,Elena Guido Vinzoni ,Gustavo Aguilar ,Andreas E Moor

Abstract

Background: Subcellular RNA localization is crucial for the spatio-temporal control of protein synthesis and underlies key processes during development, homeostasis, and disease. In epithelial cells, RNA can localize asymmetrically along the apico-basal axis. Yet, the localization of most transcripts as well as the diversity of patterns that they adopt remains unexplored. Results: Here, we use APEX-seq for proximity labeling and MERFISH for spatial transcriptomics to map subcellular transcript localization in intestinal organoids and tissue from adult mice. Many transcripts present localization bias, often localizing in granular structures. We uncover intrinsic and environmental factors that influence the formation of these patterns. Additionally, we identify translation-dependent and -independent localization patterns and pinpoint the role of 3' untranslated regions and RNA-binding proteins. Conclusions: This subcellular RNA atlas presents a detailed resource for understanding intestinal physiology. Keywords: APEX-seq; Biotinylation; Gastrointestinal tissue; MERFISH; Next-generation sequencing; Organoids; RNA granules; RNA localization; Spatial transcriptomics; Subcellular transcriptome; smFISH.

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