LINE-1 protein localization and functional dynamics during the cell cycle

Abstract

LINE-1/L1 retrotransposon sequences comprise 17% of the human genome. Among the many classes of mobile genetic elements, L1 is the only autonomous retrotransposon that still drives human genomic plasticity today. Through its co-evolution with the human genome, L1 has intertwined itself with host cell biology. However, a clear understanding of L1's lifecycle and the processes involved in restricting its insertion and intragenomic spread remains elusive. Here we identify modes of L1 proteins' entrance into the nucleus, a necessary step for L1 proliferation. Using functional, biochemical, and imaging approaches, we also show a clear cell cycle bias for L1 retrotransposition that peaks during the S phase. Our observations provide a basis for novel interpretations about the nature of nuclear and cytoplasmic L1 ribonucleoproteins (RNPs) and the potential role of DNA replication in L1 retrotransposition.

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Article and author information

Author details

  1. Paolo Mita

    Institute for Systems Genetics, Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, United States
    For correspondence
    paolo.mita@nyumc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2093-4906
  2. Aleksandra Wudzinska

    Institute for Systems Genetics, Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Xiaoji Sun

    Institute for Systems Genetics, Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Joshua Andrade

    Proteomics Laboratory, NYU Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Shruti Nayak

    Proteomics Laboratory, NYU Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. David J Kahler

    High Throughput Biology (HTB) Laboratory, NYU Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Sana Badri

    Department of Pathology, NYU Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. John LaCava

    Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6307-7713
  9. Beatrix Ueberheide

    Institute for Systems Genetics, Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Chi Y Yun

    High Throughput Biology (HTB) Laboratory, NYU Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. David Fenyö

    Institute for Systems Genetics, Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5049-3825
  12. Jef D Boeke

    Institute for Systems Genetics, Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, United States
    For correspondence
    jef.boeke@nyumc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5322-4946

Funding

National Institutes of Health (P50GM107632)

  • Jef D Boeke

National Cancer Institute (NIH/NCI P30CA16087)

  • Chi Y Yun

National Institutes of Health (1S10OD010582)

  • Chi Y Yun

NYSTEM (Contract C026719)

  • Chi Y Yun

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

Reviewing Editor

  1. Stephen P Goff, Howard Hughes Medical Institute, Columbia University, United States

Version history

  1. Received: July 1, 2017
  2. Accepted: January 4, 2018
  3. Accepted Manuscript published: January 8, 2018 (version 1)
  4. Version of Record published: February 21, 2018 (version 2)

Copyright

© 2018, Mita 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. Paolo Mita
  2. Aleksandra Wudzinska
  3. Xiaoji Sun
  4. Joshua Andrade
  5. Shruti Nayak
  6. David J Kahler
  7. Sana Badri
  8. John LaCava
  9. Beatrix Ueberheide
  10. Chi Y Yun
  11. David Fenyö
  12. Jef D Boeke
(2018)
LINE-1 protein localization and functional dynamics during the cell cycle
eLife 7:e30058.
https://doi.org/10.7554/eLife.30058

Share this article

https://doi.org/10.7554/eLife.30058

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