TY - JOUR TI - Manipulation of the human tRNA pool reveals distinct tRNA sets that act in cellular proliferation or cell cycle arrest AU - Aharon-Hefetz, Noa AU - Frumkin, Idan AU - Mayshar, Yoav AU - Dahan, Orna AU - Pilpel, Yitzhak AU - Rak, Roni A2 - Topisirovic, Ivan A2 - Cole, Philip A A2 - Topisirovic, Ivan A2 - Serrano, Luis VL - 9 PY - 2020 DA - 2020/12/24 SP - e58461 C1 - eLife 2020;9:e58461 DO - 10.7554/eLife.58461 UR - https://doi.org/10.7554/eLife.58461 AB - 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. KW - CRISPR KW - tRNA KW - cell proliferation KW - cell cycle arrest JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -