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PreprintCited by 46RNA Research and SplicingAdvanced Proteomics Techniques and ApplicationsGenomics and Chromatin Dynamics

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Concentration and dosage sensitivity of proteins driving liquid-liquid phase separation

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Farahi, Nazanin, Lazar, Tamas, Wodak, Shoshana J., Tompa, Peter, Pancsa, Rita·2021·International Journal of Molecular Sciences
DOI 10.1101/2021.02.19.430946PMC PMC8002189

Preprint — published as 10.3390/ijms22063017 · Paper page

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Abstract

Liquid-liquid phase separation (LLPS) is a molecular process that leads to the formation of membraneless organelles (MLOs), i.e. functionally specialized liquid-like cellular condensates formed by proteins and nucleic acids. Integration of data on LLPS-associated proteins from dedicated databases revealed only modest overlap between them and resulted in a confident set of 89 human LLPS driver proteins. Since LLPS is highly concentration-sensitive, the underlying experiments are often criticized for applying higher-than-physiological protein concentrations. To clarify this issue, we performed a naive comparison of in vitro applied and quantitative proteomics-derived protein concentrations and discuss a number of considerations that rationalize the choice of apparently high in vitro concentrations in most LLPS studies. The validity of in vitro LLPS experiments is further supported by in vivo phase-separation experiments and by the observation that the corresponding genes show a strong propensity for dosage sensitivity. This observation implies that the availability of the respective proteins is tightly regulated in cells to avoid erroneous condensate formation. In all, we propose that although local protein concentrations are practically impossible to determine in cells, proteomics-derived cellular concentrations should rather be considered as lower limits of protein concentrations, than strict upper bounds, to be respected by in vitro experiments.

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Metadata

Authors
Farahi, N., Lazar, T., Wodak, S. J., Tompa, P., & Pancsa, R.
Affiliations
  • Vrije Universiteit Brussel (BE)
  • Institute of Molecular Life Sciences (HU)
Corresponding author
Pancsa, Rita
ORCID
Venue
International Journal of Molecular Sciences
Publisher
openRxiv
Published
2021-02-19
Volume
22
Issue
6
Pages
3017-3017
ISSN
1422-0067 (ISSN-L)
DOI
10.1101/2021.02.19.430946
PMC
PMC8002189
OpenAlex
W3138274236
Cited by
46
References
1
Citations by year
2026: 4 · 2025: 9 · 2024: 6 · 2023: 10 · 2022: 9 · 2021: 7
FWCI
2.51
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders
  • Magyar Tudományos Akadémia (PREMIUM‐2017‐48, K124670)
  • Vrije Universiteit Brussel (SRP51)
  • Nemzeti Kutatási Fejlesztési és Innovációs Hivatal (PREMIUM-2017-48, K124670, K131702, FK128133)
  • National Research, Development and Innovation Office (K131702, K124670)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
liquid-liquid phase separation, biomolecular condensates, protein concentration, dosage sensitivity, human protein, proteomics data integration
MeSH terms
Genes, Humans, Proteins, Organelles, Databases, Factual, Gene Dosage, Proteome, Phase Transition, Molecular Sequence Annotation

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