Proteomics

Dataset Information

0

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


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. 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hek-293

DISEASE(S): Amyotrophic Lateral Sclerosis

SUBMITTER: Manfred Heller  

LAB HEAD: Marc-David Ruepp

PROVIDER: PXD015834 | Pride | 2021-09-08

REPOSITORIES: pride

Dataset's files

Source:
Action DRS
20180501_DPL1_SR_i01.raw Raw
20180501_DPL1_SR_i02.raw Raw
20180501_DPL1_SR_i03.raw Raw
20180501_DPL1_SR_i04.raw Raw
20180501_DPL3_SR_i01.raw Raw
Items per page:
1 - 5 of 122
altmetric image

Publications

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

Reber Stefan S   Jutzi Daniel D   Lindsay Helen H   Devoy Anny A   Mechtersheimer Jonas J   Levone Brunno Rocha BR   Domanski Michal M   Bentmann Eva E   Dormann Dorothee D   Mühlemann Oliver O   Barabino Silvia M L SML   Ruepp Marc-David MD  

Nucleic acids research 20210701 13


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 m  ...[more]

Similar Datasets

2021-06-23 | E-MTAB-8456 | biostudies-arrayexpress
2024-12-19 | GSE238060 | GEO
2021-04-19 | GSE144076 | GEO
2021-04-19 | GSE144642 | GEO
2023-11-08 | GSE243423 | GEO
2023-11-08 | GSE243422 | GEO
2021-03-22 | GSE138543 | GEO
2024-08-31 | GSE264392 | GEO
2024-03-18 | PXD033205 | Pride
2021-04-19 | GSE143465 | GEO