Alpha-satellite RNA transcripts are repressed by centromere-nucleolus associations

  1. Leah Bury
  2. Brittania Moodie
  3. Jimmy Ly
  4. Liliana S McKay
  5. Karen H Miga
  6. Iain M Cheeseman  Is a corresponding author
  1. Whitehead Institute, United States
  2. University of California, Santa Cruz, United States

Abstract

Although originally thought to be silent chromosomal regions, centromeres are instead actively transcribed. However, the behavior and contributions of centromere-derived RNAs have remained unclear. Here, we used single-molecule fluorescence in-situ hybridization (smFISH) to detect alpha-satellite RNA transcripts in intact human cells. We find that alpha-satellite RNA smFISH foci levels vary across cell lines and over the cell cycle, but do not remain associated with centromeres, displaying localization consistent with other long non-coding RNAs. Alpha-satellite expression occurs through RNA Polymerase II-dependent transcription, but does not require established centromere or cell division components. Instead, our work implicates centromere-nucleolar interactions as repressing alpha-satellite expression. The fraction of nucleolar-localized centromeres inversely correlates with alpha-satellite transcripts levels across cell lines and transcript levels increase substantially when the nucleolus is disrupted. The control of alpha-satellite transcripts by centromere-nucleolar contacts provides a mechanism to modulate centromere transcription and chromatin dynamics across diverse cell states and conditions.

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All data generated or analyzed during this study are included in the manuscript and supporting files.

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Author details

  1. Leah Bury

    Department of Biology, MIT, Whitehead Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Brittania Moodie

    Department of Biology, MIT, Whitehead Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jimmy Ly

    Department of Biology, MIT, Whitehead Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Liliana S McKay

    Department of Biology, MIT, Whitehead Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5426-5539
  5. Karen H Miga

    Genome Institute, University of California, Santa Cruz, Santa Cruz, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Iain M Cheeseman

    Department of Biology, MIT, Whitehead Institute, Cambridge, United States
    For correspondence
    icheese@wi.mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3829-5612

Funding

National Institute of General Medical Sciences (R35GM126930)

  • Iain M Cheeseman

American Cancer Society

  • Leah Bury

G. Harold and Leila Y. Mathers Foundation

  • Iain M Cheeseman

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

Copyright

© 2020, Bury 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. Leah Bury
  2. Brittania Moodie
  3. Jimmy Ly
  4. Liliana S McKay
  5. Karen H Miga
  6. Iain M Cheeseman
(2020)
Alpha-satellite RNA transcripts are repressed by centromere-nucleolus associations
eLife 9:e59770.
https://doi.org/10.7554/eLife.59770

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https://doi.org/10.7554/eLife.59770