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The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging
The shelterin protein complex is required for telomere protection in various eukaryotic organisms. In mammals, the shelterin subunit TRF2 is specialized in preventing ATM activation at telomeres and chromosome end fusion in somatic cells. Here, we demonstrate that the zebrafish ortholog of TRF2 (enc...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887477/ https://www.ncbi.nlm.nih.gov/pubmed/35150283 http://dx.doi.org/10.1093/nar/gkac065 |
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author | Ying, Yilin Hu, Xuefei Han, Peng Mendez-Bermudez, Aaron Bauwens, Serge Eid, Rita Tan, Li Pousse, Mélanie Giraud-Panis, Marie-Joseph Lu, Yiming Gilson, Eric Ye, Jing |
author_facet | Ying, Yilin Hu, Xuefei Han, Peng Mendez-Bermudez, Aaron Bauwens, Serge Eid, Rita Tan, Li Pousse, Mélanie Giraud-Panis, Marie-Joseph Lu, Yiming Gilson, Eric Ye, Jing |
author_sort | Ying, Yilin |
collection | PubMed |
description | The shelterin protein complex is required for telomere protection in various eukaryotic organisms. In mammals, the shelterin subunit TRF2 is specialized in preventing ATM activation at telomeres and chromosome end fusion in somatic cells. Here, we demonstrate that the zebrafish ortholog of TRF2 (encoded by the terfa gene) is protecting against unwanted ATM activation genome-wide. The terfa-compromised fish develop a prominent and specific embryonic neurodevelopmental failure. The heterozygous fish survive to adulthood but exhibit a premature aging phenotype. The recovery from embryonic neurodevelopmental failure requires both ATM inhibition and transcriptional complementation of neural genes. Furthermore, restoring the expression of TRF2 in glial cells rescues the embryonic neurodevelopment phenotype. These results indicate that the shelterin subunit TRF2 evolved in zebrafish as a general factor of genome maintenance and transcriptional regulation that is required for proper neurodevelopment and normal aging. These findings uncover how TRF2 links development to aging by separate functions in gene expression regulation and genome stability control. |
format | Online Article Text |
id | pubmed-8887477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-88874772022-03-02 The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging Ying, Yilin Hu, Xuefei Han, Peng Mendez-Bermudez, Aaron Bauwens, Serge Eid, Rita Tan, Li Pousse, Mélanie Giraud-Panis, Marie-Joseph Lu, Yiming Gilson, Eric Ye, Jing Nucleic Acids Res Genome Integrity, Repair and Replication The shelterin protein complex is required for telomere protection in various eukaryotic organisms. In mammals, the shelterin subunit TRF2 is specialized in preventing ATM activation at telomeres and chromosome end fusion in somatic cells. Here, we demonstrate that the zebrafish ortholog of TRF2 (encoded by the terfa gene) is protecting against unwanted ATM activation genome-wide. The terfa-compromised fish develop a prominent and specific embryonic neurodevelopmental failure. The heterozygous fish survive to adulthood but exhibit a premature aging phenotype. The recovery from embryonic neurodevelopmental failure requires both ATM inhibition and transcriptional complementation of neural genes. Furthermore, restoring the expression of TRF2 in glial cells rescues the embryonic neurodevelopment phenotype. These results indicate that the shelterin subunit TRF2 evolved in zebrafish as a general factor of genome maintenance and transcriptional regulation that is required for proper neurodevelopment and normal aging. These findings uncover how TRF2 links development to aging by separate functions in gene expression regulation and genome stability control. Oxford University Press 2022-02-12 /pmc/articles/PMC8887477/ /pubmed/35150283 http://dx.doi.org/10.1093/nar/gkac065 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Ying, Yilin Hu, Xuefei Han, Peng Mendez-Bermudez, Aaron Bauwens, Serge Eid, Rita Tan, Li Pousse, Mélanie Giraud-Panis, Marie-Joseph Lu, Yiming Gilson, Eric Ye, Jing The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging |
title | The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging |
title_full | The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging |
title_fullStr | The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging |
title_full_unstemmed | The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging |
title_short | The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging |
title_sort | non-telomeric evolutionary trajectory of trf2 in zebrafish reveals its specific roles in neurodevelopment and aging |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887477/ https://www.ncbi.nlm.nih.gov/pubmed/35150283 http://dx.doi.org/10.1093/nar/gkac065 |
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