G-quadruplexes sequester free heme in living cells
Abstract Heme is an essential cofactor for many enzymes, but free heme is toxic and its levels are tightly regulated. G-quadruplexes bind heme avidlyin vitro, raising the possibility that they may sequester hemein vivo. If so, then treatment that displaces heme from quadruplexes is predicted to induce expression of genes involved in iron and heme homeostasis. Here we show that PhenDC3, a G-quadruplex ligand structurally unrelated to heme, displaces quadruplex-bound hemein vitroand alters transcription in cultured human cells, up-regulating genes that support heme degradation and iron homeostasis, and most strikingly causing a 30-fold induction of heme oxidase 1, the key enzyme in heme degradation. We propose that G-quadruplexes sequester heme to protect cells from the pathophysiological consequences of free heme. This identifies a new function for G-quadruplexes and a new mechanism for protection of cells from heme..
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Preprint| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
bioRxiv.org - (2020) vom: 16. Dez. Zur Gesamtaufnahme - year:2020 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gray, Lucas T. [VerfasserIn] |
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| Links: |
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| doi: |
10.1101/652297 |
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XBI000530018 |
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| 520 | |a Abstract Heme is an essential cofactor for many enzymes, but free heme is toxic and its levels are tightly regulated. G-quadruplexes bind heme avidlyin vitro, raising the possibility that they may sequester hemein vivo. If so, then treatment that displaces heme from quadruplexes is predicted to induce expression of genes involved in iron and heme homeostasis. Here we show that PhenDC3, a G-quadruplex ligand structurally unrelated to heme, displaces quadruplex-bound hemein vitroand alters transcription in cultured human cells, up-regulating genes that support heme degradation and iron homeostasis, and most strikingly causing a 30-fold induction of heme oxidase 1, the key enzyme in heme degradation. We propose that G-quadruplexes sequester heme to protect cells from the pathophysiological consequences of free heme. This identifies a new function for G-quadruplexes and a new mechanism for protection of cells from heme. | ||
| 700 | 1 | |a Lombardi, Emilia Puig |e verfasserin |4 aut | |
| 700 | 1 | |a Verga, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Guetta, Corinne |e verfasserin |4 aut | |
| 700 | 1 | |a Nicolas, Alain |e verfasserin |4 aut | |
| 700 | 1 | |a Teulade-Fichou, Marie-Paule |e verfasserin |4 aut | |
| 700 | 1 | |a Londoño-Vallejo, Arturo |e verfasserin |4 aut | |
| 700 | 1 | |a Maizels, Nancy |e verfasserin |4 aut | |
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