Evidence map›Paper›PMID 34233002›Full record

ArticleNucleic acids research2021

The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation.

Stefan Reber, Daniel Jutzi, Helen Lindsay, Anny Devoy, Jonas Mechtersheimer, Brunno Rocha Levone, Michal Domanski, Eva Bentmann, Dorothee Dormann, Oliver Mühlemann and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. [Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. RNA G-Quadruplexes Function as a Tunable Switch of FUS Phase Separation.bioRxiv : the preprint server for biology · 2025
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 4 countries.

Stefan ReberUnited Kingdom Dementia Research Institute Centre at King's College London, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK.ORCID 0000-0002-4885-3550
Daniel JutziUnited Kingdom Dementia Research Institute Centre at King's College London, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK.ORCID 0000-0001-8381-7830
Helen LindsayDepartment of Mathematics, École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Anny DevoyUnited Kingdom Dementia Research Institute Centre at King's College London, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK.ORCID 0000-0002-1293-0630
Jonas MechtersheimerUnited Kingdom Dementia Research Institute Centre at King's College London, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK.ORCID 0000-0001-8818-7671
Brunno Rocha LevoneDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.ORCID 0000-0003-3368-4261
Michal DomanskiDepartment of Chemistry and Biochemistry, University of Bern, Bern, Switzerland.ORCID 0000-0001-6892-1496
Eva BentmannBiomedical Center (BMC), Cell Biology, Ludwig Maximilians University Munich, Germany.
Dorothee DormannBiomedical Center (BMC), Cell Biology, Ludwig Maximilians University Munich, Germany.ORCID 0000-0002-9260-2775
Oliver MühlemannDepartment of Chemistry and Biochemistry, University of Bern, Bern, Switzerland.ORCID 0000-0003-0657-1368
Silvia M L BarabinoDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.ORCID 0000-0003-3584-4417
Marc-David RueppUnited Kingdom Dementia Research Institute Centre at King's College London, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK.ORCID 0000-0003-3264-9800
King's College London · GBUniversity of Bern · CHUniversity of Milano-Bicocca · ITÉcole Polytechnique Fédérale de Lausanne · CHLudwig-Maximilians-Universität München · DEMunich Cluster for Systems Neurology · DE

Funding

Medical Research Council MR/S025898/1
6 · The paper itself

Abstract

Liquid-liquid phase separation (LLPS) of proteins and RNAs has emerged as the driving force underlying the formation of membrane-less organelles. Such biomolecular condensates have various biological functions and have been linked to disease. The protein Fused in Sarcoma (FUS) undergoes LLPS and mutations in FUS have been causally linked to the motor neuron disease Amyotrophic Lateral Sclerosis (ALS-FUS). LLPS followed by aggregation of cytoplasmic FUS has been proposed to be a crucial disease mechanism. However, it is currently unclear how LLPS impacts the behaviour of FUS in cells, e.g. its interactome. Hence, we developed a method allowing for the purification of LLPS FUS-containing droplets from cell lysates. We observe substantial alterations in the interactome, depending on its biophysical state. While non-LLPS FUS interacts mainly with factors involved in pre-mRNA processing, LLPS FUS predominantly binds to proteins involved in chromatin remodelling and DNA damage repair. Interestingly, also mitochondrial factors are strongly enriched with LLPS FUS, providing a potential explanation for the observed changes in mitochondrial gene expression in mouse models of ALS-FUS. In summary, we present a methodology to investigate the interactomes of phase separating proteins and provide evidence that LLPS shapes the FUS interactome with implications for function and disease.

Indexed as

Cell NucleusChromatinCytoplasmCytoplasmic GranulesHEK293 CellsHeLa CellsHumansProtein Interaction MappingRNA-Binding Protein FUSRNA, MessengerRNA, Small NuclearChromatinRNA-Binding Protein FUSRNA, MessengerRNA, Small Nuclear

Identifiers

PMID34233002
PMCPMC8287939
OpenAlexW2979390823

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.