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Peer-reviewedCC BY-NC-ND 4.0Nature Neuroscience

Spatial mapping of RNA turnover kinetics in the mouse brain

  • Qi Qiu1,2
  • Hongjie Zhang1,2
  • Zijie Xia1,2
  • William Gao1,2
  • Julia I. Leu1,2
  • Dongming Liang1,2
  • Ying Li1,2
  • Fan Li1,2
  • Yijing Su2,3,4
  • Emily Feierman1,2
  • Erin Van Horn1,2
  • Guo-li Ming3,5,6,7
4 more authors
  • Erica Korb1,2
  • Hongjun Song2,3,5,6,8
  • Zhaolan Zhou1,2,3
  • Hao Wu1,2,6
8 affiliations
  1. 1Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
  2. 2Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
  3. 3Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
  4. 4Department of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA USA
  5. 5Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
  6. 6Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA USA
  7. 7Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
  8. 8Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
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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 upregulation 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.

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Cite

BibTeXRIS
BibTeX
@article{qiu2026spatial,
  title = {{Spatial mapping of RNA turnover kinetics in the mouse brain}},
  author = {Qi Qiu and Hongjie Zhang and Zijie Xia and William Gao and Julia I. Leu and Dongming Liang and Ying Li and Fan Li and Yijing Su and Emily Feierman and Erin Van Horn and Guo-li Ming and Erica Korb and Hongjun Song and Zhaolan Zhou and Hao Wu},
  journal = {Nature Neuroscience},
  year = {2026},
  month = aug,
  doi = {10.1038/s41593-026-02420-y},
  url = {https://doi.org/10.1038/s41593-026-02420-y},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Spatial mapping of RNA turnover kinetics in the mouse brain
AU  - Qi Qiu
AU  - Hongjie Zhang
AU  - Zijie Xia
AU  - William Gao
AU  - Julia I. Leu
AU  - Dongming Liang
AU  - Ying Li
AU  - Fan Li
AU  - Yijing Su
AU  - Emily Feierman
AU  - Erin Van Horn
AU  - Guo-li Ming
AU  - Erica Korb
AU  - Hongjun Song
AU  - Zhaolan Zhou
AU  - Hao Wu
PY  - 2026
DA  - 2026/08/31
JO  - Nature Neuroscience
DO  - 10.1038/s41593-026-02420-y
UR  - https://doi.org/10.1038/s41593-026-02420-y
AB  - 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 upregulation 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.
SN  - 1097-6256
SN  - 1546-1726
ER  -