Evidence map›Paper›PMID 29677515›Full record

ArticleCell2018

FUS Phase Separation Is Modulated by a Molecular Chaperone and Methylation of Arginine Cation-π Interactions.

Seema Qamar, GuoZhen Wang, Suzanne J Randle, Francesco Simone Ruggeri, Juan A Varela, Julie Qiaojin Lin, Emma C Phillips, Akinori Miyashita, Declan Williams, Florian Ströhl and 14 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 513 papers.

0numbers the graph read from it
0cells of the map it votes in
513citing papers in PubMed
37.7field-weighted citation impact, top 1% 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

513 citing papers in PubMed, 918 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Review
  6. Article
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  8. Review
  9. Review
  10. Review
  11. G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  12. Review
  13. Review
  14. Article
  15. Controlling the Guanidinium Cation Rotation by Cation-π Interactions.Angewandte Chemie (International ed. in English) · 2026
    Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. ACS omega · 2026
    Article

453 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

24 authors at 5 institutions in 4 countries.

Seema QamarCambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
GuoZhen WangCambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Suzanne J RandleCambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Francesco Simone RuggeriDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Juan A VarelaDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Julie Qiaojin LinDepartment of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
Emma C PhillipsCambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Akinori MiyashitaTanz Centre for Research in Neurodegenerative Diseases and Departments of Medicine, Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3H2, Canada.
Declan WilliamsTanz Centre for Research in Neurodegenerative Diseases and Departments of Medicine, Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3H2, Canada.
Florian StröhlDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, UK.
William MeadowsCambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Rodylyn FerryTanz Centre for Research in Neurodegenerative Diseases and Departments of Medicine, Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3H2, Canada.
Victoria J DardovDepartment of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
Gian G TartagliaCentre for Genomic Regulation, the Barcelona Institute for Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra, 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.
Lindsay A FarrerDepartments of Medicine, Neurology, and Ophthalmology and Departments of Epidemiology and Biostatistics, Boston University, Boston, MA 02118, USA.
Gabriele S Kaminski SchierleDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, UK.
Clemens F KaminskiDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, UK.
Christine E HoltDepartment of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
Paul E FraserTanz Centre for Research in Neurodegenerative Diseases and Departments of Medicine, Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3H2, Canada.
Gerold Schmitt-UlmsTanz Centre for Research in Neurodegenerative Diseases and Departments of Medicine, Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3H2, Canada.
David KlenermanDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Tuomas KnowlesDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK; Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK.
Michele VendruscoloDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Peter St George-HyslopCambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK; Tanz Centre for Research in Neurodegenerative Diseases and Departments of Medicine, Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3H2, Canada. Electronic address: p.hyslop@utoronto.ca.
University of Cambridge · GBUniversity of Toronto · CABoston University · USCedars-Sinai Medical Center · USInstitució Catalana de Recerca i Estudis Avançats · ES

Funding

Biotechnology and Biological Sciences Research Council BB/H023917/1European Research Council 322817Medical Research Council G0902243Medical Research Council MR/K02292X/1Medical Research Council MR/N012453/1Wellcome Trust 203249/Z/16/Z
6 · The paper itself

Abstract

Reversible phase separation underpins the role of FUS in ribonucleoprotein granules and other membrane-free organelles and is, in part, driven by the intrinsically disordered low-complexity (LC) domain of FUS. Here, we report that cooperative cation-π interactions between tyrosines in the LC domain and arginines in structured C-terminal domains also contribute to phase separation. These interactions are modulated by post-translational arginine methylation, wherein arginine hypomethylation strongly promotes phase separation and gelation. Indeed, significant hypomethylation, which occurs in FUS-associated frontotemporal lobar degeneration (FTLD), induces FUS condensation into stable intermolecular β-sheet-rich hydrogels that disrupt RNP granule function and impair new protein synthesis in neuron terminals. We show that transportin acts as a physiological molecular chaperone of FUS in neuron terminals, reducing phase separation and gelation of methylated and hypomethylated FUS and rescuing protein synthesis. These results demonstrate how FUS condensation is physiologically regulated and how perturbations in these mechanisms can lead to disease.

Indexed as

Amyotrophic Lateral SclerosisAnimalsArginineCationsDNA MethylationFrontotemporal DementiaFrontotemporal Lobar DegenerationHumansMicroscopy, Atomic ForceMicroscopy, FluorescenceMolecular ChaperonesProtein BindingProtein DomainsProtein Processing, Post-TranslationalProtein Structure, SecondaryRNA-Binding Protein FUSArginineCationsFUS protein, humanMolecular ChaperonesRNA-Binding Protein FUSTyrosineAFM-IRarginine methylationcation-πcitrullinationfrontotemporal dementiamembraneless organelleneuronal ribonucleoprotein granulephase-sensitive fluorescent dyesphase separationsynaptic new protein synthesis

Identifiers

PMID29677515
PMCPMC5927716
OpenAlexW2802667264

What OpenQuestion holds

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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.