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Increased processing of SINE B2 ncRNAs unveils a novel type of transcriptome deregulation in amyloid beta neuropathology

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Cite this article as: eLife 2020;9:e61265 doi: 10.7554/eLife.61265

Abstract

The functional importance of many non-coding RNAs (ncRNAs) generated by repetitive elements and their connection with pathologic processes remains elusive. B2 RNAs, a class of ncRNAs of the B2 family of SINE repeats, mediate through their processing the transcriptional activation of various genes in response to stress. Here we show that this response is dysfunctional during amyloid beta toxicity and pathology in the mouse hippocampus due to increased levels of B2 RNA processing, leading to constitutively elevated B2 RNA target gene expression and high Trp53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in hippocampal cells, and is activated during amyloid toxicity, accelerating the processing of SINE RNAs and gene hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer's disease (AD).

Article and author information

Author details

  1. Yubo Cheng

    Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Luke Saville

    Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9480-1268
  3. Babita Gollen

    Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Christopher Isaac

    Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Abel Belay

    Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Jogender Mehla

    Canadian Centre for Behavioral Neuroscience, University of Lethbridge, Lethbridge, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Kush Patel

    Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Nehal Thakor

    Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Majid H Mohajerani

    Canadian Centre for Behavioral Neuroscience, University of Lethbridge, Lethbridge, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0964-2977
  10. Athanasios Zovoilis

    Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada
    For correspondence
    athanasios.zovoilis@uleth.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6425-0402

Funding

Alberta Innovates - Health Solutions

  • Majid H Mohajerani

Alzheimer Society of Alberta and Northwestern Territories

  • Majid H Mohajerani

Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada

  • Athanasios Zovoilis

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

Ethics

Animal experimentation: All experimental procedures were approved by the institutional animal care committee protocol number1404 and performed in accordance with the standards set out by the Canadian Council for Animal Care.,

Reviewing Editor

  1. Joaquín M Espinosa, University of Colorado Anschutz Medical Campus, United States

Publication history

  1. Received: July 20, 2020
  2. Accepted: November 15, 2020
  3. Accepted Manuscript published: November 16, 2020 (version 1)

Copyright

© 2020, Cheng 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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