Manipulation of the human tRNA pool reveals distinct tRNA sets that act in cellular proliferation or cell cycle arrest.
Manipulation of the human tRNA pool reveals distinct tRNA sets that act in cellular proliferation or cell cycle arrest.
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作者：
Aharon-Hefetz N;Frumkin I;Mayshar Y;Dahan O;Pilpel Y;Rak R
人类细胞中tRNA库的不同亚群在不同的细胞条件下表达。“增殖- trna”在正常细胞和癌细胞分裂时被诱导，而“分化- trna”在非分裂、分化的细胞中活跃。在这里，我们研究了各种trna在细胞生长和阻滞中的重要性。我们建立了一个基于crispr的编辑程序，每个sgrna靶向一个tRNA家族。我们测量了tRNA对细胞生长的重要性，发现在快速生长的细胞系中，与分化tRNA相比，大多数增殖tRNA是必不可少的。然而，在更缓慢的分界线中，分化trna更为重要。此外，我们测量了每个tRNA家族对细胞周期阻滞信号的反应的重要性。在这里，我们发现了一种更复杂的行为，增殖trna和分化trna都表现出不同程度的重要性。这些结果提供了迄今为止最全面的人类trna在各种细胞状态下具有复杂作用的功能表征。
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.