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

  1. Noa Aharon-Hefetz
  2. Idan Frumkin
  3. Yoav Mayshar
  4. Orna Dahan  Is a corresponding author
  5. Yitzhak Pilpel  Is a corresponding author
  6. Roni Rak
  1. Weizmann Institute of Science, Israel

Abstract

Different subsets of the tRNA pool in human 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.

Data availability

Source data files have been provided for Figure 1.Sequencing data are available in GEO under the accession code GSE163611

The following data sets were generated

Article and author information

Author details

  1. Noa Aharon-Hefetz

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Idan Frumkin

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Yoav Mayshar

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Orna Dahan

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    Orna.Dahan@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.
  5. Yitzhak Pilpel

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    Pilpel@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3200-9344
  6. Roni Rak

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.

Funding

The Israel Science Foundation

  • Yitzhak Pilpel

European Research Council

  • Yitzhak Pilpel

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ivan Topisirovic, Jewish General Hospital, Canada

Publication history

  1. Received: April 30, 2020
  2. Accepted: December 18, 2020
  3. Accepted Manuscript published: December 24, 2020 (version 1)
  4. Version of Record published: January 4, 2021 (version 2)

Copyright

© 2020, Aharon-Hefetz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Noa Aharon-Hefetz
  2. Idan Frumkin
  3. Yoav Mayshar
  4. Orna Dahan
  5. Yitzhak Pilpel
  6. Roni Rak
(2020)
Manipulation of the human tRNA pool reveals distinct tRNA sets that act in cellular proliferation or cell cycle arrest
eLife 9:e58461.
https://doi.org/10.7554/eLife.58461

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