Abstract
Subcellular RNA localization is a fundamental layer of gene regulation, yet its heterogeneity across individual cells remains poorly understood. Here, we introduce the RNA Localization Profiler (RLP), a proximity-based RNA-editing strategy that maps compartment-specific RNAs in living cells. Across the cytoplasm, endoplasmic reticulum (ER), and plasma membrane, RLP identifies robust and highly specific RNA localization programs linked to translation and membrane organization. Single-cell RLP (scRLP) reveals that individual cells harbor roughly 5,000-7,000 cytoplasmic RNAs, with <10% associated with the ER. These measurements uncover pervasive subcellular heterogeneity in RNA localization that is undetectable by bulk assays. Spatial RNA patterns define an orthogonal axis of cell-state identity that is independent of gene expression. For example, ZWINT mRNA relocalizes to the cytoplasm in a cell cycle-dependent manner. These findings establish heterogeneous levels of subcellular RNA localization as a variable dimension of intracellular organization and cell identity.
Full text
1,194 characters
· extracted from
oa-doi-fallback
· click to expand
Abstract
Subcellular RNA localization is a fundamental layer of gene regulation, yet its heterogeneity across individual cells remains poorly understood. Here, we introduce the RNA Localization Profiler (RLP), a proximity-based RNA-editing strategy that maps compartment-specific RNAs in living cells. Across the cytoplasm, endoplasmic reticulum (ER), and plasma membrane, RLP identifies robust and highly specific RNA localization programs linked to translation and membrane organization. Single-cell RLP (scRLP) reveals that individual cells harbor roughly 5,000-7,000 cytoplasmic RNAs, with <10% associated with the ER. These measurements uncover pervasive subcellular heterogeneity in RNA localization that is undetectable by bulk assays. Spatial RNA patterns define an orthogonal axis of cell-state identity that is independent of gene expression. For example, ZWINT mRNA relocalizes to the cytoplasm in a cell cycle-dependent manner. These findings establish heterogeneous levels of subcellular RNA localization as a variable dimension of intracellular organization and cell identity.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵2 Lead Contact
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.