1. Cell Biology
Download icon

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

  1. Paolo Mita  Is a corresponding author
  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  Is a corresponding author
  1. NYU Langone Medical Center, United States
  2. The Rockefeller University, United States
Research Article
  • Cited 34
  • Views 5,207
  • Annotations
Cite this article as: eLife 2018;7:e30058 doi: 10.7554/eLife.30058

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.

Data availability

The following data sets were generated

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

Publication 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.

Metrics

  • 5,207
    Page views
  • 896
    Downloads
  • 34
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Genetics and Genomics
    Sandra L Martin
    Insight

    The mechanisms by which a retrotransposon called LINE-1 duplicates itself and spreads through the human genome are becoming clearer.

    1. Cell Biology
    Jennifer M Kunselman et al.
    Research Article Updated

    Many signal transduction systems have an apparent redundancy built into them, where multiple physiological agonists activate the same receptors. Whether this is true redundancy, or whether this provides an as-yet unrecognized specificity in downstream signaling, is not well understood. We address this question using the kappa opioid receptor (KOR), a physiologically relevant G protein-coupled receptor (GPCR) that is activated by multiple members of the Dynorphin family of opioid peptides. We show that two related peptides, Dynorphin A and Dynorphin B, bind and activate KOR to similar extents in mammalian neuroendocrine cells and rat striatal neurons, but localize KOR to distinct intracellular compartments and drive different post-endocytic fates of the receptor. Strikingly, localization of KOR to the degradative pathway by Dynorphin A induces sustained KOR signaling from these compartments. Our results suggest that seemingly redundant endogenous peptides can fine-tune signaling by regulating the spatiotemporal profile of KOR signaling.