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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
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.
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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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