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

Noa Aharon-Hefetz; Idan Frumkin; Orna Dahan; Yitzhak Pilpel; Roni Rak

doi:10.7554/eLife.58461

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

Noa Aharon-Hefetz, Idan Frumkin, Orna Dahan, Yitzhak Pilpel, Roni Rak

Department of Molecular Genetics

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e58461
Number of pages	28
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.58461
State	Published - 24 Dec 2020

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10.7554/eLife.58461License: CC BY

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title = "Manipulation of the human tRNA pool reveals distinct tRNA sets that act in cellular proliferation or cell cycle arrest",

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.",

author = "Noa Aharon-Hefetz and Idan Frumkin and Orna Dahan and Yitzhak Pilpel and Roni Rak",

note = "We thank the Israel Science Foundation and the European Research Council for grant support. We wish to thank Tammy Biniashvili and Omer Asraf for the help with the deep-sequencing analyses. We thank Dr. Tomer Meir Salame from The Weizmann Institute of Science's Flow Cytometry Core Facility for the help with the Flow Cytometry experiments. We thank Lior Roitman and Dr. Hilah Gal from Prof. Valery Krizhanovsky group from the Weizmann Institute of Science for the help and guidance with the cell cycle arrest experiments. Special thanks for Prof. George Church (Harvard Medical School) and Prof. Moshe Oren (Weizmann Institute of Science) for their kind contributions of cell lines and plasmids. A special thank for Dr. Hila Gingold and the Pilpel lab, for the stimulating discussions. Funding - Israel Science Foundation (1332/14) -Yitzhak Pilpel European Research Council (616622) - Yitzhak Pilpel",

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AU - Pilpel, Yitzhak

AU - Rak, Roni

N1 - We thank the Israel Science Foundation and the European Research Council for grant support. We wish to thank Tammy Biniashvili and Omer Asraf for the help with the deep-sequencing analyses. We thank Dr. Tomer Meir Salame from The Weizmann Institute of Science's Flow Cytometry Core Facility for the help with the Flow Cytometry experiments. We thank Lior Roitman and Dr. Hilah Gal from Prof. Valery Krizhanovsky group from the Weizmann Institute of Science for the help and guidance with the cell cycle arrest experiments. Special thanks for Prof. George Church (Harvard Medical School) and Prof. Moshe Oren (Weizmann Institute of Science) for their kind contributions of cell lines and plasmids. A special thank for Dr. Hila Gingold and the Pilpel lab, for the stimulating discussions. Funding - Israel Science Foundation (1332/14) -Yitzhak Pilpel European Research Council (616622) - Yitzhak Pilpel

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

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