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对人类 tRNA 池的操纵揭示了在细胞增殖或细胞周期停滞中起作用的不同 tRNA 集。

Manipulation of the human tRNA pool reveals distinct tRNA sets that act in cellular proliferation or cell cycle arrest.

机构信息

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

出版信息

Elife. 2020 Dec 24;9:e58461. doi: 10.7554/eLife.58461.

DOI:10.7554/eLife.58461
PMID:33357381
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7781600/
Abstract

Different subsets of the tRNA pool in human cells are expressed in different cellular conditions. The 'proliferation-tRNAs' are induced upon normal and cancerous cell division, while the 'differentiation-tRNAs' are active in non-dividing, differentiated cells. Here we examine the essentiality of the various tRNAs upon cellular growth and arrest. We established a CRISPR-based editing procedure with sgRNAs that each target a tRNA family. We measured tRNA essentiality for cellular growth and found that most proliferation-tRNAs are essential compared to differentiation- tRNAs in rapidly growing cell lines. Yet in more slowly dividing lines, the differentiation-tRNAs were more essential. In addition, we measured the essentiality of each tRNA family upon response to cell cycle arresting signals. Here we detected a more complex behavior with both proliferation-tRNAs and differentiation tRNAs showing various levels of essentiality. These results provide the so-far most comprehensive functional characterization of human tRNAs with intricate roles in various cellular states.

摘要

不同亚群的 tRNA 在人类细胞中表达于不同的细胞状态。“增殖-tRNA”在正常和癌变细胞分裂时被诱导,而“分化-tRNA”在非分裂、分化的细胞中活跃。在此,我们研究了各种 tRNA 在细胞生长和停滞时的必要性。我们建立了一种基于 CRISPR 的编辑程序,使用 sgRNA 靶向每个 tRNA 家族。我们测量了 tRNA 对细胞生长的必要性,发现与分化-tRNA 相比,大多数增殖-tRNA 在快速生长的细胞系中是必需的。然而,在分裂较慢的细胞系中,分化-tRNA 更为必需。此外,我们测量了每个 tRNA 家族在响应细胞周期阻滞信号时的必要性。在这里,我们检测到一种更复杂的行为,增殖-tRNA 和分化-tRNA 表现出不同程度的必需性。这些结果提供了迄今为止最全面的人类 tRNA 功能特征,揭示了其在各种细胞状态下复杂的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2a/7781600/c113d502257d/elife-58461-fig5-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2a/7781600/20914ff81590/elife-58461-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2a/7781600/361826f4ba22/elife-58461-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2a/7781600/fe1294f8e362/elife-58461-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2a/7781600/2059fa79d6f4/elife-58461-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2a/7781600/d279d32641e6/elife-58461-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2a/7781600/f239d27c1bb7/elife-58461-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c2a/7781600/8edea5a7401f/elife-58461-fig4-figsupp1.jpg
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