The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging.
The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging.
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斑马鱼TRF2的非端粒进化轨迹揭示了其在神经发育和衰老中的特定作用
DOI：
10.1093/nar/gkac065
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发表时间：
2022-02-28
影响因子：
14.9
通讯作者：
Ye J
中科院分区：
文献类型：
--
作者：
Ying Y;Hu X;Han P;Mendez-Bermudez A;Bauwens S;Eid R;Tan L;Pousse M;Giraud-Panis MJ;Lu Y;Gilson E;Ye J
摘要在多种真核生物中，谢尔特林蛋白复合体是端粒保护所必需的。在哺乳动物中，Shelterin亚单位TRF2专门用于阻止体细胞中端粒ATM的激活和染色体末端的融合。在这里，我们证明了斑马鱼TRF2的同源基因(由Terfa基因编码)正在保护整个基因组免受不必要的ATM激活。特尔法受损的鱼会出现明显的、特定的胚胎神经发育障碍。杂合子的鱼可以活到成年，但表现出过早衰老的表型。从胚胎神经发育衰竭中恢复需要ATM抑制和神经基因的转录互补。此外，恢复TRF2在神经胶质细胞中的表达可以挽救胚胎的神经发育表型。这些结果表明，隐藏蛋白亚基TRF2在斑马鱼中进化为基因组维持和转录调节的通用因子，这是正常神经发育和正常衰老所必需的。这些发现揭示了TRF2如何通过基因表达调控和基因组稳定性控制中的不同功能将发育与衰老联系起来。
Abstract 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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影响因子：
16.8
作者：
Mendez-Bermudez, Aaron;Giraud-Panis, Marie-Josephe;Gilson, Eric
通讯作者：
Gilson, Eric
影响因子：
5
作者：
Morgan, R. Garrett;Walker, Ashley E.;Donato, Anthony J.
通讯作者：
Donato, Anthony J.
NBS1 磷酸化状态决定功能失调端粒的修复选择
影响因子：
16
作者：
Rai R;Hu C;Broton C;Chen Y;Lei M;Chang S
通讯作者：
Chang S
影响因子：
64.8
作者：
Okamoto, Keiji;Bartocci, Cristina;Ouzounov, Iliana;Diedrich, Jolene K.;Yates, John R., III;Denchi, Eros Lazzerini
通讯作者：
Denchi, Eros Lazzerini
影响因子：
2.6
作者：
Andræ, J;Bongcam-Rudloff, E;Nistér, M
通讯作者：
Nistér, M