Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 67

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Tau‐induced nuclear envelope invagination causes a toxic accumulation of mRNA in Drosophila

Cornelison, Garrett L., Levy, Simon A., Jenson, Tyler, Frost, Bess·2019·Aging Cell
DOI 10.1111/acel.12847PMC PMC6351838
Open this paper in CoChat — free account

Abstract

The nucleus is a spherical dual‐membrane bound organelle that encapsulates genomic DNA. In eukaryotes, messenger RNAs (mRNA) are transcribed in the nucleus and transported through nuclear pores into the cytoplasm for translation into protein. In certain cell types and pathological conditions, nuclei harbor tubular invaginations of the nuclear envelope known as the “nucleoplasmic reticulum.” Nucleoplasmic reticulum expansion has recently been established as a mediator of neurodegeneration in tauopathies, including Alzheimer's disease. While the presence of pore‐lined, cytoplasm‐filled, nuclear envelope invaginations has been proposed to facilitate the rapid export of RNAs from the nucleus to the cytoplasm, the functional significance of nuclear envelope invaginations in regard to RNA export in any disorder is currently unknown. Here, we report that polyadenylated RNAs accumulate within and adjacent to tau‐induced nuclear envelope invaginations in a Drosophila model of tauopathy. Genetic or pharmacologic inhibition of RNA export machinery reduces accumulation of polyadenylated RNA within and adjacent to nuclear envelope invaginations and reduces tau‐induced neuronal death. These data are the first to point toward a possible role for RNA export through nuclear envelope invaginations in the pathogenesis of a neurodegenerative disorder and suggest that nucleocytoplasmic transport machinery may serve as a possible novel class of therapeutic targets for the treatment of tauopathies.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/acel.12847

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Polyadenylated RNA accumulates at nuclear invaginations in tau transgenic Drosophila. (a) Immunostaining of Lamin and fluorescence in situ hybridization of polyadenylated RNA with a poly(dT) nucleotide probe in control and tau transgenic Drosophila brains. Arrowhead indicates nuclear invaginations. (b) Comparison of extranuclear versus intra‐invagination accumulation of polyadenylated RNA in nuclei of tau transgenic Drosophila brains. Arrowhead indicates extranuclear accumulation of polyadenylated RNA, while arrow indicates intra‐invagination accumulation of polyadenylated RNA. (c) Pie chart depicting the percent of invaginated nuclei in tau transgenic Drosophila that are associated with either extranuclear, intra‐invagination, or no polyadenylated RNA accumulation, n = 4, 100 nuclei per fly. All flies are 10 days old. Control is elav‐Gal4/+. Scale bars represent 5 μm
Figure 1 Polyadenylated RNA accumulates at nuclear invaginations in tau transgenic Drosophila. (a) Immunostaining of Lamin and fluorescence in situ hybridization of polyadenylated RNA with a poly(dT) nucleotide probe in control and tau transgenic Drosophila brains. Arrowhead indicates nuclear invaginations. (b) Comparison of extranuclear versus intra‐invagination accumulation of polyadenylated RNA in nuclei of tau transgenic Drosophila brains. Arrowhead indicates extranuclear accumulation of polyadenylated RNA, while arrow indicates intra‐invagination accumulation of polyadenylated RNA. (c) Pie chart depicting the percent of invaginated nuclei in tau transgenic Drosophila that are associated with either extranuclear, intra‐invagination, or no polyadenylated RNA accumulation, n = 4, 100 nuclei per fly. All flies are 10 days old. Control is elav‐Gal4/+. Scale bars represent 5 μmCC BY · PubMed Central
Figure 2 Genetic or pharmacologic inhibition of RNA export machinery reduces tau‐induced toxicity in vivo. (a) Neuronal degeneration assayed by TUNEL staining; n = 6. (b) Western blot showing human tau protein levels in Drosophila heads. Representative images (c) and quantification (d) of the fraction of nuclear invaginations associated with RNA accumulation in Drosophila brains harboring the indicated allele or transgene; n = 4, 100 nuclei per fly. (e) Neuronal degeneration assayed by TUNEL staining in tau transgenic Drosophila treated with either 500 nM leptomycin B (Lept.), 500 nM KPT 350, or the appropriate vehicle. (f) Western blot showing tau protein levels in tau transgenic Drosophila treated with leptomycin B (Lept.), KPT350, or the appropriate vehicle. Arrowheads indicate Lamin invaginations. All flies are 10 days old. Controls are elav‐Gal4/+. Data are presented as the mean ± sem; unpaired t test or ANOVA with Dunnett's post hoc test, *p < 0.05; ***p < 0.001; ****p < 0.0001
Figure 2 Genetic or pharmacologic inhibition of RNA export machinery reduces tau‐induced toxicity in vivo. (a) Neuronal degeneration assayed by TUNEL staining; n = 6. (b) Western blot showing human tau protein levels in Drosophila heads. Representative images (c) and quantification (d) of the fraction of nuclear invaginations associated with RNA accumulation in Drosophila brains harboring the indicated allele or transgene; n = 4, 100 nuclei per fly. (e) Neuronal degeneration assayed by TUNEL staining in tau transgenic Drosophila treated with either 500 nM leptomycin B (Lept.), 500 nM KPT 350, or the appropriate vehicle. (f) Western blot showing tau protein levels in tau transgenic Drosophila treated with leptomycin B (Lept.), KPT350, or the appropriate vehicle. Arrowheads indicate Lamin invaginations. All flies are 10 days old. Controls are elav‐Gal4/+. Data are presented as the mean ± sem; unpaired t test or ANOVA with Dunnett's post hoc test, *p < 0.05; ***p < 0.001; ****p < 0.0001CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 11

  1. 10.1038/s41593-017-0047-3 · DOI
  2. 10.1080/19491034.2016.1183859 · DOI · Paper page
  3. 10.1016/j.cub.2015.11.039 · DOI · Paper page
  4. 10.1016/j.neuron.2017.03.027 · DOI
  5. 10.1038/nn.3953 · DOI
  6. 10.1093/nar/gkw010 · DOI · Paper page
  7. 10.1016/j.tcb.2011.03.008 · DOI
  8. 10.1038/ncb2056 · DOI
  9. 10.1242/jcs.198697 · DOI
  10. 10.1016/j.jmb.2015.09.023 · DOI
  11. 10.1126/science.1062382 · DOI · Paper page

Cited by

See all 67

Metadata

Authors
Cornelison, G. L., Levy, S. A., Jenson, T., & Frost, B.
Venue
Aging Cell
Publisher
Wiley
Published
2018-11-09
Volume
18
Issue
1
ISSN
  • 1474-9718
  • 1474-9726
DOI
10.1111/acel.12847
PMC
PMC6351838
Cited by
67
References
3
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Institute on Aging (T32 AG 21890‐14)
  • National Institute of Neurological Disorders and Stroke (R00 NS 088429)
  • American Federation for Aging Research (2017 New Investigator in Alzheimer's Disease)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.