Transcriptomics

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Spatial mapping of RNA turnover kinetics in the mouse brain


ABSTRACT: Gene regulation requires coordinated control of RNA synthesis and degradation, yet measuring RNA turnover across intact tissues remains challenging. Here we present spatial NT-seq, a method that combines transgenesis-free metabolic RNA labeling with in situ chemical recoding on spatial transcriptomics platforms to co-map newly synthesized and pre-existing RNAs. Applying spatial NT-seq to the mouse brain reveals pronounced regional heterogeneity in RNA turnover and identifies the dentate gyrus as a spatial hotspot marked by coordinated up-regulation of basal RNA synthesis and decay. Moreover, spatial NT-seq uncovers rapid, brain region-specific transcriptional and post-transcriptional responses to electroconvulsive stimulation, a clinically relevant treatment for refractory depression. Finally, we leverage computational modeling to identify sequence features and post-transcriptional regulators that shape transcriptome-wide mRNA stability across spatial and cellular contexts in the mouse brain. Together, this integrated “in vivo Timescope” framework provides a spatially resolved view of RNA turnover kinetics and reveals the regulatory architecture of RNA stability in vivo.

ORGANISM(S): Mus musculus

PROVIDER: GSE249405 | GEO | 2026/06/12

REPOSITORIES: GEO

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