Preclinical study reveals regional RNA turnover kinetics and activity responses in mouse brains, highlighting the spatial architecture of transcript stability.
Key Points
To develop a method for spatially mapping RNA synthesis and decay rates across intact tissue and to characterize RNA turnover dynamics throughout the mouse brain.
Engineered spatial NT-seq by coupling transgenesis-free metabolic RNA labeling with in situ chemical recoding on spatial transcriptomics arrays.
Mapped newly synthesized and pre-existing RNA pools across intact mouse brain slices under basal conditions and following electroconvulsive stimulation.
Used computational modeling to evaluate sequence features and post-transcriptional regulators influencing mRNA stability across anatomical niches.
Spatial NT-seq revealed prominent regional heterogeneity in RNA turnover, uncovering the dentate gyrus as a kinetic hotspot with coordinated upregulation of basal synthesis and degradation.
Electroconvulsive stimulation induced immediate, region-specific transcriptional and post-transcriptional kinetic alterations throughout the brain.
Computational modeling identified discrete transcript sequence features and regulatory factors governing spatial mRNA stability in vivo.