Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich, Switzerland.
EMBO J. 2011 Aug 9;30(19):4047-58. doi: 10.1038/emboj.2011.280.
Eukaryotic up-frameshift 1 (UPF1) is a nucleic acid-dependent ATPase and 5'-to-3' helicase, best characterized for its roles in cytoplasmic RNA quality control. We previously demonstrated that human UPF1 binds to telomeres in vivo and its depletion leads to telomere instability. Here, we show that UPF1 is present at telomeres at least during S and G2/M phases and that UPF1 association with telomeres is stimulated by the phosphoinositide 3-kinase (PI3K)-related protein kinase ataxia telangiectasia mutated and Rad3-related (ATR) and by telomere elongation. UPF1 physically interacts with the telomeric factor TPP1 and with telomerase. Akin to UPF1 binding to telomeres, this latter interaction is mediated by ATR. Moreover, the ATPase activity of UPF1 is required to prevent the telomeric defects observed upon UPF1 depletion, and these defects stem predominantly from inefficient telomere leading-strand replication. Our results portray a scenario where UPF1 orchestrates crucial aspects of telomere biology, including telomere replication and telomere length homeostasis.
真核生物移码 1（UPF1）是一种依赖核酸的 ATP 酶和 5'-3'解旋酶，其在细胞质 RNA 质量控制中的作用最为突出。我们之前的研究表明，人类 UPF1 在体内与端粒结合，其耗竭会导致端粒不稳定。在这里，我们表明 UPF1 至少在 S 和 G2/M 期存在于端粒上，并且 UPF1 与端粒的结合受到磷酸肌醇 3-激酶（PI3K）相关蛋白激酶共济失调毛细血管扩张突变和 Rad3 相关（ATR）以及端粒伸长的刺激。UPF1 与端粒因子 TPP1 和端粒酶发生物理相互作用。与 UPF1 与端粒的结合类似，这种相互作用是由 ATR 介导的。此外，UPF1 的 ATP 酶活性对于防止 UPF1 耗竭后观察到的端粒缺陷是必需的，这些缺陷主要源于端粒前导链复制效率低下。我们的研究结果描绘了一个场景，其中 UPF1 协调端粒生物学的关键方面，包括端粒复制和端粒长度稳态。
