scholarly journals Biomolecular condensates as arbiters of biochemical reactions inside the nucleus

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Guillaume Laflamme ◽  
Karim Mekhail
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Environmental Conditions ◽  
Genome Organization ◽  
Liquid Phase Separation ◽  
Nuclear Space ◽  
Biological Processes ◽  
Biochemical Reactions ◽  
Dynamic Structures ◽  
Liquid Liquid Phase Separation

AbstractLiquid-liquid phase separation (LLPS) has emerged as a central player in the assembly of membraneless compartments termed biomolecular condensates. These compartments are dynamic structures that can condense or dissolve under specific conditions to regulate molecular functions. Such properties allow biomolecular condensates to rapidly respond to changing endogenous or environmental conditions. Here, we review emerging roles for LLPS within the nuclear space, with a specific emphasis on genome organization, expression and repair. Our review highlights the emerging notion that biomolecular condensates regulate the sequential engagement of molecules in multistep biological processes.

scholarly journals Observation of liquid-liquid phase separation of ataxin-3 and quantitative evaluation of its concentration in a single droplet using Raman microscopy

2021 ◽  
Author(s):  
Kazuki Murakami ◽  
Shinji Kajimoto ◽  
Daiki Shibata ◽  
Kunisato Kuroi ◽  
Fumihiko Fujii ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Quantitative Evaluation ◽  
Raman Microscopy ◽  
Liquid Phase Separation ◽  
Biological Processes ◽  
Single Droplet ◽  
Liquid Liquid Phase Separation

Liquid–liquid phase separation (LLPS) plays an important role in a variety of biological processes and is also associated with protein aggregation in neurodegenerative diseases. Quantification of LLPS is necessary to...

scholarly journals The (un)structural biology of biomolecular liquid-liquid phase separation using NMR spectroscopy

2020 ◽  
Vol 295 (8) ◽  
pp. 2375-2384 ◽  
Author(s):  
Anastasia C. Murthy ◽  
Nicolas L. Fawzi
Keyword(s):  
Phase Separation ◽  
Nmr Spectroscopy ◽  
Liquid Phase ◽  
Structural Biology ◽  
Liquid Phase Separation ◽  
Biological Processes ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Molecular Aspects ◽  
Liquid Liquid Phase Separation

Liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a phenomenon that underlies membraneless compartmentalization of the cell. The underlying molecular interactions that underpin biomolecular LLPS have been of increased interest due to the importance of membraneless organelles in facilitating various biological processes and the disease association of several of the proteins that mediate LLPS. Proteins that are able to undergo LLPS often contain intrinsically disordered regions and remain dynamic in solution. Solution-state NMR spectroscopy has emerged as a leading structural technique to characterize protein LLPS due to the variety and specificity of information that can be obtained about intrinsically disordered sequences. This review discusses practical aspects of studying LLPS by NMR, summarizes recent work on the molecular aspects of LLPS of various protein systems, and discusses future opportunities for characterizing the molecular details of LLPS to modulate phase separation.

Dynamic behavior of liquid droplets with enzyme compartmentalization triggered by sequential glycolytic enzyme reactions

2021 ◽  
Author(s):  
Tomoto Ura ◽  
Shunsuke Tomita ◽  
Kentaro Shiraki
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Dynamic Behavior ◽  
Droplet Formation ◽  
Glycolytic Enzyme ◽  
Liquid Phase Separation ◽  
Biological Processes ◽  
Liquid Droplets ◽  
Enzyme Reactions ◽  
Liquid Liquid Phase Separation

Dynamic droplet formation via liquid-liquid phase separation (LLPS) is believed to be involved in the regulation of various biological processes. Here, a model LLPS system coupled with a sequential glycolytic...

scholarly journals Suppression of liquid-liquid phase separation by 1,6-hexanediol partially compromises the 3D genome organization in living cells

2020 ◽  
Author(s):  
Sergey V. Ulianov ◽  
Artem K. Velichko ◽  
Mikhail D. Magnitov ◽  
Artem V. Luzhin ◽  
Arkadiy K. Golov ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Spatial Organization ◽  
Living Cells ◽  
Liquid Phase Separation ◽  
Nuclear Space ◽  
3D Genome ◽  
Chromatin Folding ◽  
Optical Reconstruction ◽  
Liquid Liquid Phase Separation

AbstractLiquid-liquid phase separation (LLPS) contributes to the spatial and functional segregation of molecular processes. However, the role played by LLPS in chromatin folding in living cells remains unclear. Here, using stochastic optical reconstruction microscopy (STORM) and Hi-C techniques, we studied the effects of 1,6-hexanediol (1,6-HD)-mediated LLPS modulation on higher-order chromatin organization in living cells. We found that 1,6-HD treatment caused the enlargement of nucleosome nanodomains and their more uniform distribution in the nuclear space. At a megabase-scale, chromatin underwent moderate but irreversible perturbations that resulted in the partial mixing of A and B compartments. The removal of 1,6-HD from the culture medium did not allow chromatin to acquire initial configurations, but increased further mixing of the chromatin compartments and resulted in more compact repressed chromatin than in untreated cells. 1,6-HD treatment also weakened enhancer-promoter interactions but did not considerably affect CTCF-dependent loops. Our results suggest that 1,6-HD-sensitive LLPS plays a limited role in chromatin spatial organization by constraining its folding patterns and facilitating compartmentalization at different levels.

scholarly journals LncRNAs: Architectural Scaffolds or More Potential Roles in Phase Separation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Luo ◽  
Lei Qu ◽  
Feiran Gao ◽  
Jun Lin ◽  
Jian Liu ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Biological Activities ◽  
Disease Diagnosis ◽  
Liquid Phase Separation ◽  
Diagnosis And Treatment ◽  
Biological Processes ◽  
And Function ◽  
Liquid Liquid Phase Separation

Biomolecules specifically aggregate in the cytoplasm and nucleus, driving liquid-liquid phase separation (LLPS) formation and diverse biological processes. Extensive studies have focused on revealing multiple functional membraneless organelles in both the nucleus and cytoplasm. Condensation compositions of LLPS, such as proteins and RNAs affecting the formation of phase separation, have been gradually unveiled. LncRNAs possessing abundant second structures usually promote phase separation formation by providing architectural scaffolds for diverse RNAs and proteins interaction in both the nucleus and cytoplasm. Beyond scaffolds, lncRNAs may possess more diverse functions, such as functioning as enhancer RNAs or buffers. In this review, we summarized current studies on the function of phase separation and its related lncRNAs, mainly in the nucleus. This review will facilitate our understanding of the formation and function of phase separation and the role of lncRNAs in these processes and related biological activities. A deeper understanding of the formation and maintaining of phase separation will be beneficial for disease diagnosis and treatment.

scholarly journals Characterization of Liquid-liquid phase Separation in 3D Genome Organization

2020 ◽  
Author(s):  
Tingting Li ◽  
Jiaqing Xing ◽  
Tao Li ◽  
Teng Li ◽  
Weihua Li
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Genome Organization ◽  
Enrichment Analysis ◽  
Liquid Phase Separation ◽  
Rna Recognition Motif ◽  
3D Genome ◽  
Shiny App ◽  
Modular Domains ◽  
Liquid Liquid Phase Separation

Abstract Many proteins have been demonstrated to participate in 3D genome organization through liquid-liquid phase separation (LLPS) such as RNPII, HP1a. However, systematic investigation of relationships between LLPS and 3D genome organization remains lacking. Here, we predicted the intrinsic disordered regions (IDRs) and modular domains of all human proteins and performed GSEA analysis according to their proportions of IDRs. Our results showed that main biological processes involved in 3D genome organization are highly enriched with IDRs, including chromatin organization, RNA splicing and histone modification, demonstrating the key role of LLPS in regulating nuclear structure. Of the 3885 IDR-rich proteins, 1427 proteins are involved in 3D genome organization. IDR regions of these proteins have strong preference of Ser, Leu, Pro, Ala, Gly, Glu and Lys, and lack of hydrophobic amino acids such as Trp, Tyr, Phe and Met, suggesting dipolar interactions rather than aromatic-involved interactions involved. Further motif enrichment analysis suggests that RNA recognition motif and zinc finger motif are the two most abundant repeatedly-occurred modular domains within IDR-containing proteins. Finally, we developed a Shiny APP named phasepro that interactively analyze and visualize a protein’s potential of LLPS, including IDRs, motifs, amino acid preferences and electric charges.

scholarly journals Suppression of liquid–liquid phase separation by 1,6-hexanediol partially compromises the 3D genome organization in living cells

2021 ◽  
Author(s):  
Sergey V Ulianov ◽  
Artem K Velichko ◽  
Mikhail D Magnitov ◽  
Artem V Luzhin ◽  
Arkadiy K Golov ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Spatial Organization ◽  
Living Cells ◽  
Liquid Phase Separation ◽  
Nuclear Space ◽  
3D Genome ◽  
Chromatin Folding ◽  
Optical Reconstruction ◽  
Liquid Liquid Phase Separation

Abstract Liquid–liquid phase separation (LLPS) contributes to the spatial and functional segregation of molecular processes within the cell nucleus. However, the role played by LLPS in chromatin folding in living cells remains unclear. Here, using stochastic optical reconstruction microscopy (STORM) and Hi-C techniques, we studied the effects of 1,6-hexanediol (1,6-HD)-mediated LLPS disruption/modulation on higher-order chromatin organization in living cells. We found that 1,6-HD treatment caused the enlargement of nucleosome clutches and their more uniform distribution in the nuclear space. At a megabase-scale, chromatin underwent moderate but irreversible perturbations that resulted in the partial mixing of A and B compartments. The removal of 1,6-HD from the culture medium did not allow chromatin to acquire initial configurations, and resulted in more compact repressed chromatin than in untreated cells. 1,6-HD treatment also weakened enhancer-promoter interactions and TAD insulation but did not considerably affect CTCF-dependent loops. Our results suggest that 1,6-HD-sensitive LLPS plays a limited role in chromatin spatial organization by constraining its folding patterns and facilitating compartmentalization at different levels.

scholarly journals Liquid-Liquid Phase Separation of Tau Driven by Hydrophobic Interaction Facilitates Fibrillization of Tau

2021 ◽  
Vol 433 (2) ◽  
pp. 166731
Author(s):  
Yanxian Lin ◽  
Yann Fichou ◽  
Andrew P. Longhini ◽  
Luana C. Llanes ◽  
Pengyi Yin ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Hydrophobic Interaction ◽  
Liquid Phase Separation ◽  
Liquid Liquid Phase Separation
Sign in / Sign up

Export Citation Format

Share Document