Cyclin A2-CDK2 regulates embryonic gene activation in 1-cell mouse embryos
Cyclin A2-CDK2 regulates embryonic gene activation in 1-cell mouse embryos
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DOI：
10.1016/j.ydbio.2005.07.012
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发表时间：
2005-10-01
影响因子：
2.7
通讯作者：
Aoki, F
中科院分区：
文献类型：
--
作者：
Hara, KT;Oda, S;Aoki, F
在小鼠中母体mRNA的募集对于在1-细胞阶段开始的胚胎基因激活（EGA）是必不可少的。然而，目前尚不清楚哪些被招募的mRNA是负责的。我们在这里报告，募集细胞周期蛋白A2 mRNA可能是至关重要的EGA。细胞周期蛋白A2蛋白在受精后6 ~ 12 h（EGA启动时）在原核中积累。这种细胞周期蛋白A2可能是由母体募集的细胞周期蛋白A2 mRNA产生的，因为它的积累被抑制mRNA聚腺苷酸化的3 '-脱氧腺苷抑制。当CDK 2活性或细胞周期蛋白A2的原核积累分别用CDK 2抑制剂或显微注射siRNA抑制时，DNA复制不受抑制，但转录活性的增加被阻止。此外，显微注射重组细胞周期蛋白A2-CDK 2蛋白增加转录活性。细胞周期蛋白A2-CDK 2在卵激活后被激活，因为使用识别由该激酶催化的位点特异性磷酸化的抗体观察到视网膜母细胞瘤蛋白磷酸化的增加，并且用CDK 2抑制剂处理或用细胞周期蛋白A2 siRNA显微注射防止视网膜母细胞瘤蛋白磷酸化的增加。这些结果表明，招聘的母亲细胞周期蛋白A2 mRNA卵子激活与EGA。(c)2005年爱思唯尔公司All rights reserved.
Recruitment of maternal mRNA in mice appears essential for embryonic gene activation (EGA) that is initiated in the 1-cell stage. The identity of which recruited mRNAs is responsible, however, is not known. We report here that recruitment of cyclin A2 mRNA may be critical for EGA. Cyclin A2 protein accumulates in pronuclei between 6 and 12 h after fertilization, the time when EGA is initiated. This cyclin A2 may be generated from maternally recruited cyclin A2 mRNA because its accumulation was inhibited by 3'-deoxyadenosine, which inhibits mRNA polyadenylation. When CDK2 activity or pronuclear accumulation of cyclin A2 was inhibited with CDK2 inhibitors or by microinjected siRNAs, respectively, DNA replication was not inhibited but the increase of transcriptional activity was prevented. In addition, microinjection of recombinant cyclin A2-CDK2 protein increased transcriptional activity. Cyclin A2-CDK2 is activated following egg activation, because an increase in phosphorylation of retinoblastoma protein was observed using antibodies that recognize site-specific phosphorylation catalyzed by this kinase and treatment with a CDK2 inhibitor or microinjection with cyclin A2 siRNAs prevented the increase in retinoblastoma protein phosphorylation. These results suggest that recruitment of maternal cyclin A2 mRNA following egg activation is linked to EGA. (c) 2005 Elsevier Inc. All rights reserved.