Long noncoding RNA DREAMer bridges the DREAM complex and E2f1 to regulate endoreplication in Drosophila

IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Dong Li, Tianyu Jin, Jun Liu, Chunlin Lu, Xianmei Yang, Haiyan Zhang, Limin Bi, Yuhang Yan, Lijiao Zhang, Yan Sang, Bilian Jin, Xiaolin Bi
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Abstract

Rb/E2f and DREAM complexes play vital roles in regulating cell cycle progression. To date, how they coordinate their functions to regulate cell cycle–dependent gene expression is not clear. Here, we identified a long noncoding RNA (lncRNA), which we named DREAMer, that bridges the interaction between E2f1 and the dREAM complex to regulate endoreplication specifically in Drosophila salivary gland. We show that E2f1 directly stimulates DREAMer expression, whereas DREAMer mediates the repression of e2f1 transcription by modulating the recruitment of the dREAM complex to the e2f1 promoter via a direct interaction with the dREAM component E2f2. The depletion of DREAMer impairs dREAM binding, leading to derepression of e2f1 transcription, which ultimately increases E2f1 activity and promotes the endoreplication. Furthermore, the transcriptomic analysis revealed profound changes in cell cycle–related gene expression in DREAMerKO salivary glands. Together, our findings reveal an lncRNA-mediated link between the dREAM complex and E2f1, which regulates endoreplication during development.
长非编码 RNA DREAMer 可连接 DREAM 复合物和 E2f1,从而调节果蝇的内复制。
Rb/E2f 和 DREAM 复合物在调节细胞周期进程中发挥着重要作用。迄今为止,它们如何协调其功能以调控细胞周期依赖性基因表达还不清楚。在这里,我们发现了一种长非编码 RNA(lncRNA),并将其命名为 DREAMer,它是 E2f1 和 dREAM 复合物之间相互作用的桥梁,能特异性地调控果蝇唾液腺的内再复制。我们的研究表明,E2f1直接刺激DREAMer的表达,而DREAMer则通过与dREAM成分E2f2直接相互作用,调节dREAM复合体对E2f1启动子的招募,从而介导对E2f1转录的抑制。DREAMer 的耗竭会损害 dREAM 的结合,导致 e2f1 转录的抑制减弱,最终增加 E2f1 的活性并促进内再复制。此外,转录组分析还揭示了 DREAMerKO唾液腺中细胞周期相关基因表达的深刻变化。总之,我们的研究结果揭示了 dREAM 复合物与 E2f1 之间由 lncRNA 介导的联系,后者在发育过程中调控内再复制。
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来源期刊
Science Advances
Science Advances 综合性期刊-综合性期刊
CiteScore
21.40
自引率
1.50%
发文量
1937
审稿时长
29 weeks
期刊介绍: Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.
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