Genetically encoded fluorescent reporter for polyamines
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 targetin...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60147-z |
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| author | 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 |
| author_facet | 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 |
| author_sort | Pushkal Sharma |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4350da2ac1a3424caa28bc65932cbce7 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4350da2ac1a3424caa28bc65932cbce72025-08-20T03:22:07ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-60147-zGenetically encoded fluorescent reporter for polyaminesPushkal Sharma0Colin Y. Kim1Heather R. Keys2Shinya Imada3Alex B. Joseph4Luke Ferro5Tenzin Kunchok6Rachel Anderson7Yulin Sun8Ömer H. Yilmaz9Jing-Ke Weng10Ankur Jain11Whitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical ResearchThe David H. Koch Institute for Integrative Cancer Research at MITWhitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical ResearchInstitute for Plant-Human Interface, Northeastern UniversityThe David H. Koch Institute for Integrative Cancer Research at MITWhitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical ResearchAbstract 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.https://doi.org/10.1038/s41467-025-60147-z |
| spellingShingle | 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 Genetically encoded fluorescent reporter for polyamines Nature Communications |
| title | Genetically encoded fluorescent reporter for polyamines |
| title_full | Genetically encoded fluorescent reporter for polyamines |
| title_fullStr | Genetically encoded fluorescent reporter for polyamines |
| title_full_unstemmed | Genetically encoded fluorescent reporter for polyamines |
| title_short | Genetically encoded fluorescent reporter for polyamines |
| title_sort | genetically encoded fluorescent reporter for polyamines |
| url | https://doi.org/10.1038/s41467-025-60147-z |
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