The translational landscape of the mammalian cell cycle.

The translational landscape of the mammalian cell cycle.
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DOI:
10.1016/j.molcel.2013.09.018
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发表时间:
2013-11-21
期刊:
影响因子:
16
通讯作者:
Ruggero, Davide
Ruggero, Davide
中科院分区:
生物学1区
文献类型:
--
作者:
Stumpf, Craig R.;Moreno, Melissa V.;Olshen, Adam B.;Taylor, Barry S.;Ruggero, Davide

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细胞周期进程中的基因调控是一个复杂的编排过程,确保准确的DNA复制和分裂。然而,基因表达的翻译景观的细胞周期进展仍然在很大程度上未知。在这里,采用全基因组核糖体分析,我们发现了广泛的翻译调控的数百种mRNA作为一个意想不到的机制,基因调控的细胞周期进程的基础。一个突出的例子是RICTOR的S期翻译调节,其与mTORC2信号传导的细胞周期依赖性激活和准确的细胞周期进展相关。我们进一步确定了在致力于细胞周期进程、脂质代谢和基因组完整性的分子复合物内mRNA翻译控制中未被重视的协调。这包括大多数mRNA,其包含控制基因组组织的粘附素和凝聚素复合物,其通过其5′ UTR在特定的细胞周期阶段中协调控制。我们的研究结果阐明了哺乳动物细胞周期中翻译调控的普遍性和动态性。
Gene regulation during cell cycle progression is an intricately choreographed process, ensuring accurate DNA replication and division. However, the translational landscape of gene expression underlying cell cycle progression remains largely unknown. Here, employing genome-wide ribosome profiling we uncover widespread translational regulation of hundreds of mRNAs serving as an unexpected mechanism for gene regulation underlying cell cycle progression. A striking example is the S-phase translational regulation of RICTOR, which is associated with cell cycle-dependent activation of mTORC2 signaling and accurate cell cycle progression. We further identified unappreciated coordination in translational control of mRNAs within molecular complexes dedicated to cell cycle progression, lipid metabolism, and genome integrity. This includes the majority of mRNAs comprising the cohesin and condensin complexes, controlling genome organization, which are coordinately translationally controlled in specific cell cycle phases via their 5′ UTRs. Our findings illuminate the prevalence and dynamic nature of translational regulation underlying the mammalian cell cycle.
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