Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression
Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression
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DOI：
10.1016/j.bbrc.2012.02.007
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发表时间：
2012-03-09
影响因子：
3.1
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
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作者：
Takahashi, Akinori;Kikuguchi, Chisato;Yamamoto, Tadashi
基因表达的稳定性影响基因表达的动态化。CCR4-NOT复合体是哺乳动物细胞中的主要死烯基酶，它缩短了mRNA聚(A)尾巴，导致了mRNAs的失稳。CCR4-NOT复合体在细胞增殖、细胞凋亡和新陈代谢等多种生理功能中发挥着重要作用。在这里，我们证明了CCR4-Not复合体的一个亚单位CNOT3参与了纺锤体组装检查点的调节，这表明CCR4-Not复合体也在有丝分裂的调节中发挥作用。CNOT3缺失增加了有丝分裂停滞细胞的数量，并特异性地增加了在纺锤体组装检查点中起作用的MAD1mRNA及其蛋白产物的表达。我们发现，CNOT3缺失可以稳定MAD1mRNA，而MAD1基因敲除可以减弱CNOT3缺失导致的有丝分裂指数的增加。基于这些观察，我们认为CNOT3通过调节MAD！的稳定性参与了纺锤体组装检查点的调节。MRNA.(C)2012 Elsevier Inc.保留所有权利。
The stability of mRNA influences the dynamics of gene expression. The CCR4-NOT complex, the major deadenylase in mammalian cells, shortens the mRNA poly(A) tail and contributes to the destabilization of mRNAs. The CCR4-NOT complex plays pivotal roles in various physiological functions, including cell proliferation, apoptosis, and metabolism. Here, we show that CNOT3, a subunit of the CCR4-NOT complex, is involved in the regulation of the spindle assembly checkpoint, suggesting that the CCR4-NOT complex also plays a part in the regulation of mitosis. CNOT3 depletion increases the population of mitotic-arrested cells and specifically increases the expression of MAD1 mRNA and its protein product that plays a part in the spindle assembly checkpoint. We showed that CNOT3 depletion stabilizes the MAD1 mRNA, and that MAD1 knockdown attenuates the CNOT3 depletion-induced increase of the mitotic index. Basing on these observations, we propose that CNOT3 is involved in the regulation of the spindle assembly checkpoint through its ability to regulate the stability of MAD! mRNA. (C) 2012 Elsevier Inc. All rights reserved.