Author
Listed:
- Pushkal Sharma
(Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology)
- Colin Y. Kim
(Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology
Harvard University)
- Heather R. Keys
(Whitehead Institute for Biomedical Research)
- Shinya Imada
(The David H. Koch Institute for Integrative Cancer Research at MIT)
- Alex B. Joseph
(Whitehead Institute for Biomedical Research)
- Luke Ferro
(Whitehead Institute for Biomedical Research)
- Tenzin Kunchok
(Whitehead Institute for Biomedical Research)
- Rachel Anderson
(Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology)
- Yulin Sun
(Northeastern University
Northeastern University
Northeastern University
Northeastern University)
- Ömer H. Yilmaz
(The David H. Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology)
- Jing-Ke Weng
(Whitehead Institute for Biomedical Research
Northeastern University
Northeastern University
Northeastern University)
- Ankur Jain
(Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology)
Abstract
Polyamines are abundant and evolutionarily conserved metabolites that are essential for life. Dietary polyamine supplementation extends life-span and health-span. Dysregulation of polyamine homeostasis is linked to Parkinson’s disease and cancer, driving interest in therapeutically targeting this pathway. However, measuring cellular polyamine levels, which vary across cell types and states, remains challenging. We introduce a genetically encoded polyamine reporter for real-time measurement of polyamine concentrations in single living cells. This reporter utilizes the polyamine-responsive ribosomal frameshift motif from the OAZ1 gene. We demonstrate broad applicability of this approach and reveal dynamic changes in polyamine levels in response to genetic and pharmacological perturbations. Using this reporter, we conduct a genome-wide CRISPR screen and uncover an unexpected link between mitochondrial respiration and polyamine import, which are both risk factors for Parkinson’s disease. By offering a lens to examine polyamine biology, this reporter may advance our understanding of these ubiquitous metabolites and accelerate therapy development.
Suggested Citation
Pushkal Sharma & Colin Y. Kim & Heather R. Keys & Shinya Imada & Alex B. Joseph & Luke Ferro & Tenzin Kunchok & Rachel Anderson & Yulin Sun & Ömer H. Yilmaz & Jing-Ke Weng & Ankur Jain, 2025.
"Genetically encoded fluorescent reporter for polyamines,"
Nature Communications, Nature, vol. 16(1), pages 1-16, December.
Handle:
RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60147-z
DOI: 10.1038/s41467-025-60147-z
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