Cited by 151RNA Research and SplicingGenetic Neurodegenerative DiseasesGenetics and Neurodevelopmental Disorders

MBNL Sequestration by Toxic RNAs and RNA Misprocessing in the Myotonic Dystrophy Brain

Open access
Goodwin, Marianne, Mohan, Apoorva, Batra, Ranjan, Lee, Kuang-Yung, Charizanis, Konstantinos, Gómez, Francisco José Fernández, Eddarkaoui, Sabiha, Sergeant, Nicolas +11 more·2015·Cell Reports

Abstract

For some neurological disorders, disease is primarily RNA mediated due to expression of non-coding microsatellite expansion RNAs (RNA(exp)). Toxicity is thought to result from enhanced binding of proteins to these expansions and depletion from their normal cellular targets. However, experimental evidence for this sequestration model is lacking. Here, we use HITS-CLIP and pre-mRNA processing analysis of human control versus myotonic dystrophy (DM) brains to provide compelling evidence for this RNA toxicity model. MBNL2 binds directly to DM repeat expansions in the brain, resulting in depletion from its normal RNA targets with downstream effects on alternative splicing and polyadenylation. Similar RNA processing defects were detected in Mbnl compound-knockout mice, highlighted by dysregulation of Mapt splicing and fetal tau isoform expression in adults. These results demonstrate that MBNL proteins are directly sequestered by RNA(exp) in the DM brain and introduce a powerful experimental tool to evaluate RNA-mediated toxicity in other expansion diseases.

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 · 10.1016/j.celrep.2015.07.029

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

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?

  • In myotonic dystrophy, CTG or CCTG repeat expansions in expressed RNAs sequester MBNL proteins from their normal binding sites, altering MBNL-dependent splicing patterns.

    “In myotonic dystrophy, CTG or CCTG repeat expansions in expressed RNAs sequester MBNL proteins from their normal binding sites, altering MBNL-dependent splicing patterns101–105.”

    From The neurogenetics of alternative splicing (2016) · cites this paper as [105]

  • MBNL activity controls alternative polyadenylation events.

    “recent studies of Mbnl1/2 dKOs have highlighted MBNL activity in controlling alternative polyadenylation events105,107,108.”

    From The neurogenetics of alternative splicing (2016) · cites this paper as [105]

Self-check

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

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

Cites

Flagged first, then by citations

2 of the 49 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Goodwin, M., Mohan, A., Batra, R., Lee, K.-Y., Charizanis, K., Gómez, F. J. F., Eddarkaoui, S., Sergeant, N., Buée, L., Kimura, T., Clark, H. B., Dalton, J., Takamura, K., Weyn-Vanhentenryck, S. M., Zhang, C., Reid, T., Ranum, L. P. W., Day, J. W., & Swanson, M. S.
Affiliations
  • University of Florida (US)
  • Chang Gung Memorial Hospital (TW)
  • Inserm (FR)
  • Hyogo Medical University (JP)
  • University of Minnesota (US)
  • Columbia University (US)
  • Stanford Medicine (US)
Corresponding author
Swanson, Maurice S.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2015-08
Volume
12
Issue
7
Pages
1159-1168
ISSN
2211-1247 (ISSN-L)
OpenAlex
W1664710634
Cited by
151
References
49
Citations by year
2026: 10 · 2025: 16 · 2024: 7 · 2023: 15 · 2022: 19 · 2021: 12 · 2020: 12 · 2019: 11 · 2018: 24 · 2017: 13 · 2016: 12
FWCI
7.10
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • ARC Centre for Nanoscale BioPhotonics
  • National Institutes of Health
  • U.S. Public Health Service (GSE68890)
  • National Institute of General Medical Sciences (R00GM095713)
  • National Institute of Neurological Disorders and Stroke (P01NS058901, NS058901, R01NS089676)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR046799)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
myotonic dystrophy, MBNL proteins, MBNL2, alternative splicing, polyadenylation, pre-mRNA processing, tau isoforms, RNA-binding proteins, HITS-CLIP
MeSH terms
Animals, Brain, DNA-Binding Proteins, Humans, Myotonic Dystrophy, RNA Splicing, RNA-Binding Proteins, tau Proteins, Microsatellite Repeats, RNA, Untranslated, DNA Repeat Expansion, Mice

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