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

Abstract
Data availability
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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).

Data availability

Short and long-RNA-seq data have been deposited to GEO with access number GSE149243.

The following data sets were generated

(2020) Increased processing of SINE B2 non coding RNAs unveils a novel type of transcriptome de-regulation underlying amyloid beta neuro-pathology
NCBI Gene Expression Omnibus, GSE149243.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149243

The following previously published data sets were used

1. Mahat DB
2. Salamanca HH
3. Duarte FM
4. Danko CG
5. Lis JT.
(2016) Mammalian Heat Shock Response and Mechanisms Underlying Its Genome-wide Transcriptional Regulation
NCBI Gene Expression Omnibus, GSE71708.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71708

Article and author information

Author details

Yubo Cheng

Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada

Competing interests
The authors declare that no competing interests exist.
Luke Saville

Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9480-1268
Babita Gollen

Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada

Competing interests
The authors declare that no competing interests exist.
Christopher Isaac

Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada

Competing interests
The authors declare that no competing interests exist.
Abel Belay

Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada

Competing interests
The authors declare that no competing interests exist.
Jogender Mehla

Canadian Centre for Behavioral Neuroscience, University of Lethbridge, Lethbridge, Canada

Competing interests
The authors declare that no competing interests exist.
Kush Patel

Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada

Competing interests
The authors declare that no competing interests exist.
Nehal Thakor

Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Canada

Competing interests
The authors declare that no competing interests exist.
Majid H Mohajerani

Canadian Centre for Behavioral Neuroscience, University of Lethbridge, Lethbridge, Canada

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0964-2977
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.

"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.,

Copyright

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.