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Cited by 71RNA Research and SplicingAmyotrophic Lateral Sclerosis ResearchRNA regulation and disease

TDP‐1, the Caenorhabditis elegans ortholog of TDP‐43, limits the accumulation of double‐stranded RNA

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Saldi, Tassa K, Ash, Peter EA, Wilson, Gavin, Gonzales, Patrick, Garrido‐Lecca, Alfonso, Roberts, Christine M, Dostal, Vishantie, Gendron, Tania F +4 more·2014·The EMBO Journal
DOI 10.15252/embj.201488740PMC PMC4282642
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Abstract

Caenorhabditis elegans mutants deleted for TDP-1, an ortholog of the neurodegeneration-associated RNA-binding protein TDP-43, display only mild phenotypes. Nevertheless, transcriptome sequencing revealed that many RNAs were altered in accumulation and/or processing in the mutant. Analysis of these transcriptional abnormalities demonstrates that a primary function of TDP-1 is to limit formation or stability of double-stranded RNA. Specifically, we found that deletion of tdp-1: (1) preferentially alters the accumulation of RNAs with inherent double-stranded structure (dsRNA); (2) increases the accumulation of nuclear dsRNA foci; (3) enhances the frequency of adenosine-to-inosine RNA editing; and (4) dramatically increases the amount of transcripts immunoprecipitable with a dsRNA-specific antibody, including intronic sequences, RNAs with antisense overlap to another transcript, and transposons. We also show that TDP-43 knockdown in human cells results in accumulation of dsRNA, indicating that suppression of dsRNA is a conserved function of TDP-43 in mammals. Altered accumulation of structured RNA may account for some of the previously described molecular phenotypes (e.g., altered splicing) resulting from reduction of TDP-43 function.

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  • Knockout of the C. elegans tdp1 ortholog or of TDP-43 in human cells results in dsRNA accumulation, including sequences that map to TEs.

    “Knockout of the C. elegans tdp1 ortholog or of TDP-43 in human cells also results in dsRNA accumulation, including sequences that map to TEs”

    From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Saldi et al. 2014

    The Abstract reports that deletion of worm tdp-1 increases dsRNA, including transposon transcripts. The Results section, “Limiting dsRNA accumulation is a conserved function of human TDP-43,” reports increased dsRNA from the HERV-K retrotransposon in human cells after TDP-43 knockdown. The claim is inaccurate in calling the human-cell experiment a knockout. (LLM, conf=0.90)

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References 65 · Cited by 71

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Authors
Saldi, T. K., Ash, P. E., Wilson, G., Gonzales, P., Garrido‐Lecca, A., Roberts, C. M., Dostal, V., Gendron, T. F., Stein, L. D., Blumenthal, T., Petrucelli, L., & Link, C. D.
Affiliations
  • University of Colorado Boulder (US)
  • Mayo Clinic (US)
  • Ontario Institute for Cancer Research (CA)
  • University of Toronto (CA)
Corresponding author
Saldi, Tassa K
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2014-11-12
Volume
33
Issue
24
Pages
2947-2966
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.15252/embj.201488740
PMC
PMC4282642
OpenAlex
W2008334829
Cited by
71
References
65
Citations by year
2026: 5 · 2025: 7 · 2024: 10 · 2023: 2 · 2022: 5 · 2021: 9 · 2020: 3 · 2019: 12 · 2018: 10 · 2017: 4 · 2016: 2 · 2015: 2
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
Locations
  • The EMBO Journal (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • NIH (NS063964, GM42432, AG026251, ES20395)
  • DOD (W81XWH‐10‐1‐0512‐1, W81XWH‐09‐1‐0315AL093108)
  • CIHR Frederick Banting and Charles Best Canada Graduate Scholarship
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
TDP-43, double-stranded RNA, RNA-binding proteins, RNA accumulation, RNA editing, adenosine-to-inosine editing, transposable elements, antisense RNA, RNA splicing, neurodegeneration, Caenorhabditis elegans, human cells
MeSH terms
Animals, DNA-Binding Proteins, Humans, RNA, Double-Stranded, RNA-Binding Proteins, Caenorhabditis elegans, Gene Deletion, Gene Expression Profiling, RNA Stability, Caenorhabditis elegans Proteins

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