The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis

  1. Roland Ivanyi-Nagy  Is a corresponding author
  2. Syed Moiz Ahmed
  3. Sabrina Peter
  4. Priya Dharshana Ramani
  5. Peh Fern Ong
  6. Oliver Dreesen
  7. Peter Dröge  Is a corresponding author
  1. Nanyang Technological University, Singapore
  2. Skin Research Institute Singapore, Singapore

Abstract

Telomerase RNA (TR) provides the template for DNA repeat synthesis at telomeres and is essential for genome stability in continuously dividing cells. We mapped the RNA interactome of human TR (hTR) and identified a set of non-coding and coding hTR-interacting RNAs, including the histone 1C mRNA (HIST1H1C). Disruption of the hTR-HIST1H1C RNA association resulted in markedly increased telomere elongation without affecting telomerase enzymatic activity. Conversely, over-expression of HIST1H1C led to telomere attrition. By using a combination of mutations to disentangle the effects of histone 1 RNA synthesis, protein expression, and hTR interaction, we show that HIST1H1C RNA negatively regulates telomere length independently of its protein coding potential. Taken together, our data provide important insights into a surprisingly complex hTR-RNA interaction network and define an unexpected non-coding RNA role for HIST1H1C in regulating telomere length homeostasis, thus offering a glimpse into the mostly uncharted, vast space of non-canonical messenger RNA functions.

Data availability

Sequencing data have been deposited in the NCBI Sequence Read Archive (SRA) under the accession code SRP123633.

The following data sets were generated

Article and author information

Author details

  1. Roland Ivanyi-Nagy

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    For correspondence
    roland.ivanyi-nagy@ntu.edu.sg
    Competing interests
    The authors declare that no competing interests exist.
  2. Syed Moiz Ahmed

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  3. Sabrina Peter

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  4. Priya Dharshana Ramani

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  5. Peh Fern Ong

    Cell Ageing, Skin Research Institute Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  6. Oliver Dreesen

    Cell Ageing, Skin Research Institute Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1148-3557
  7. Peter Dröge

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    For correspondence
    pdroge@ntu.edu.sg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5447-738X

Funding

Ministry of Education - Singapore (MOE2012-T3-1-001)

  • Peter Dröge

Singapore Biomedical Research Council

  • Oliver Dreesen

Agency for Science, Technology and Research

  • Oliver Dreesen

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

Copyright

© 2018, Ivanyi-Nagy 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. Roland Ivanyi-Nagy
  2. Syed Moiz Ahmed
  3. Sabrina Peter
  4. Priya Dharshana Ramani
  5. Peh Fern Ong
  6. Oliver Dreesen
  7. Peter Dröge
(2018)
The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis
eLife 7:e40037.
https://doi.org/10.7554/eLife.40037

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https://doi.org/10.7554/eLife.40037