Genetically encoded fluorescent reporter for polyamines

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 and Ankur Jain ()
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Pushkal Sharma: Whitehead Institute for Biomedical Research
Colin Y. Kim: Whitehead Institute for Biomedical Research
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
Yulin Sun: Northeastern University
Ömer H. Yilmaz: The David H. Koch Institute for Integrative Cancer Research at MIT
Jing-Ke Weng: Whitehead Institute for Biomedical Research
Ankur Jain: Whitehead Institute for Biomedical Research

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60147-z

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