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PXD015834 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation
DescriptionLiquid-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. One of the best studied proteins undergoing LLPS is Fused in Sarcoma (FUS), a predominantly nuclear RNA-binding protein. Mutations in FUS have been causally linked to Amyotrophic Lateral Sclerosis (ALS), an adult-onset motor neuron disease, and LLPS followed by aggregation of cytoplasmic FUS has been proposed to be a crucial disease mechanism. In spite of this, it is currently unclear how LLPS impacts the behaviour of FUS in cells, e.g. its interactome. In order to study the consequences of LLPS on FUS and its interaction partners, we developed a method that allows for the purification of phase separated FUS-containing droplets from cell lysates. We observe substantial alterations in the interactome of FUS, depending on its biophysical state. While non-phase separated FUS interacts mainly with its well-known interaction partners involved in pre-mRNA processing, phase-separated FUS predominantly binds to proteins involved in chromatin remodelling and DNA damage repair. Interestingly, factors with function in mitochondria are strongly enriched with phase-separated FUS, providing a potential explanation for early changes in mitochondrial gene expression observed in mouse models of ALS-FUS. In summary, we present a methodology that allows to investigate the interactome of phase-separating proteins and provide evidence that LLPS strongly shapes the FUS interactome with important implications for function and disease.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterManfred Heller
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-10-15 06:01:17ID requested
12022-02-15 09:24:07announced
Publication List
Reber S, Jutzi D, Lindsay H, Devoy A, Mechtersheimer J, Levone BR, Domanski M, Bentmann E, Dormann D, Mühlemann O, Barabino SML, Ruepp MD, The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation. Nucleic Acids Res, 49(13):7713-7731(2021) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: Liquid-liquid phase separation, Fused in Sarcoma, Amyotrophic Lateral Sclerosis
Contact List
Marc-David Ruepp
contact affiliationDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, 125 Coldharbour Lane, London SE5 9NU, U.K
contact emailmarc-david.ruepp@kcl.ac.uk
lab head
Manfred Heller
contact affiliationUniversity of Bern
contact emailmanfred.heller@dbmr.unibe.ch
dataset submitter
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