FUS and TDP-43 Phases in Health and Disease

A Prion Epigenetic Switch Establishes an Active Chromatin State

(2020) Zachary H. Harvey et al.   CELL

TDP-43 α-helical structure tunes liquid–liquid phase separation and function

(2020) Alexander E. Conicella et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Valence and patterning of aromatic residues determine the phase behavior of prion-like domains

(2020) Erik W. Martin et al.   SCIENCE

Poly(ADP-ribose): A Dynamic Trigger for Biomolecular Condensate Formation

(2020) Anthony K.L. Leung   TRENDS IN CELL BIOLOGY

Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization

(2020) David W. Sanders et al.   CELL

G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Granules

(2020) Peiguo Yang et al.   CELL

RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation

(2020) Jordina Guillén-Boixet et al.   CELL

Composition-dependent thermodynamics of intracellular phase separation

(2020) Joshua A. Riback et al.   NATURE

Antisense oligonucleotides for neurodegeneration

(2020) Blair R. Leavitt et al.   SCIENCE

Stress Induces Dynamic, Cytotoxicity-Antagonizing TDP-43 Nuclear Bodies via Paraspeckle LncRNA NEAT1-Mediated Liquid-Liquid Phase Separation

(2020) Chen Wang et al.   MOLECULAR CELL

Partitioning of cancer therapeutics in nuclear condensates

(2020) Isaac A. Klein et al.   SCIENCE

Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations

(2020) Ryan R Cupo et al.   eLife

An Allosteric Modulator of RNA Binding Targeting the N-Terminal Domain of TDP-43 Yields Neuroprotective Properties

(2020) Niloufar Mollasalehi et al.   ACS Chemical Biology

The prion-like domain of FUS is phosphorylated by multiple kinases affecting liquid- and solid-phase transitions

(2020) Izzy Owen et al.   MOLECULAR BIOLOGY OF THE CELL

Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency

(2020) Jiasheng Zhang et al.   NATURE

Shifts and drifts in prion science

(2020) Adriano Aguzzi et al.   SCIENCE

Nuclear Import Receptors Directly Bind to Arginine-Rich Dipeptide Repeat Proteins and Suppress Their Pathological Interactions

(2020) Saskia Hutten et al.   Cell Reports

RNA Binding Antagonizes Neurotoxic Phase Transitions of TDP-43

(2019) Jacob R. Mann et al.   NEURON

Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death

(2019) Fatima Gasset-Rosa et al.   NEURON

Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report

(2019) Peter T Nelson et al.   BRAIN

ULK1 and ULK2 Regulate Stress Granule Disassembly Through Phosphorylation and Activation of VCP/p97

(2019) Bo Wang et al.   MOLECULAR CELL

A first order phase transition mechanism underlies protein aggregation in mammalian cells

(2019) Arjun Narayanan et al.   eLife

Chronic optogenetic induction of stress granules is cytotoxic and reveals the evolution of ALS-FTD pathology

(2019) Peipei Zhang et al.   eLife

A small molecule targeting TDP-43’s RNA recognition motifs reduces locomotor defects in a Drosophila model of ALS

(2019) Liberty Francois-Moutal et al.   ACS Chemical Biology

Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD

(2019) Mark Y. Fang et al.   NEURON

Evaluating phase separation in live cells: diagnosis, caveats, and functional consequences

(2019) David T. McSwiggen et al.   GENES & DEVELOPMENT

Inherited and Sporadic Amyotrophic Lateral Sclerosis and Fronto-Temporal Lobar Degenerations arising from Pathological Condensates of Phase Separating Proteins

(2019) Michael Fernandopulle et al.   HUMAN MOLECULAR GENETICS

Loss of Dynamic RNA Interaction and Aberrant Phase Separation Induced by Two Distinct Types of ALS/FTD-Linked FUS Mutations

(2019) Amirhossein Ghanbari Niaki et al.   MOLECULAR CELL

A Non-amyloid Prion Particle that Activates a Heritable Gene Expression Program

(2019) Anupam K. Chakravarty et al.   MOLECULAR CELL

The mutational landscape of a prion-like domain

(2019) Benedetta Bolognesi et al.   Nature Communications

Phase separation-deficient TDP43 remains functional in splicing

(2019) Hermann Broder Schmidt et al.   Nature Communications

LASSI: A lattice model for simulating phase transitions of multivalent proteins

(2019) Jeong-Mo Choi et al.   PLoS Computational Biology

Relationship of Sequence and Phase Separation in Protein Low-Complexity Regions

(2018) Erik W. Martin et al.   BIOCHEMISTRY

Physical Principles and Extant Biology Reveal Roles for RNA-Containing Membraneless Compartments in Origins of Life Chemistry

(2018) Raghav R. Poudyal et al.   BIOCHEMISTRY

Functional Implications of Intracellular Phase Transitions

(2018) Alex S. Holehouse et al.   BIOCHEMISTRY

The physiological and pathological biophysics of phase separation and gelation of RNA binding proteins in amyotrophic lateral sclerosis and fronto-temporal lobar degeneration

(2018) Peter St George-Hyslop et al.   BRAIN RESEARCH

Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites

(2018) Takuya Yoshizawa et al.   CELL

Phase Separation of FUS Is Suppressed by Its Nuclear Import Receptor and Arginine Methylation

(2018) Mario Hofweber et al.   CELL

Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules

(2018) Sebastian Markmiller et al.   CELL

A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion-like RNA Binding Proteins

(2018) Jie Wang et al.   CELL

Nuclear-Import Receptors Reverse Aberrant Phase Transitions of RNA-Binding Proteins with Prion-like Domains

(2018) Lin Guo et al.   CELL

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

(2018) Seema Qamar et al.   CELL

A single N‐terminal phosphomimic disrupts TDP‐43 polymerization, phase separation, and RNA splicing

(2018) Ailin Wang et al.   EMBO JOURNAL

The Role of Post-Translational Modifications on Prion-Like Aggregation and Liquid-Phase Separation of FUS

(2018) Shannon Rhoads et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

TAR DNA-binding protein 43 (TDP-43) liquid–liquid phase separation is mediated by just a few aromatic residues

(2018) Hao-Ru Li et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Proteome-Level Analysis Indicates Global Mechanisms for Post-Translational Regulation of RRM Domains

(2018) Roman Sloutsky et al.   JOURNAL OF MOLECULAR BIOLOGY

RGG/RG Motif Regions in RNA Binding and Phase Separation

(2018) P. Andrew Chong et al.   JOURNAL OF MOLECULAR BIOLOGY

More than Just a Phase: Prions at the Crossroads of Epigenetic Inheritance and Evolutionary Change

(2018) Anupam K. Chakravarty et al.   JOURNAL OF MOLECULAR BIOLOGY

TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD

(2018) Ching-Chieh Chou et al.   NATURE NEUROSCIENCE

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation

(2018) Elizabeth L. Guenther et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Atomic structures of FUS LC domain segments reveal bases for reversible amyloid fibril formation

(2018) Feng Luo et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

RNA buffers the phase separation behavior of prion-like RNA binding proteins

(2018) Shovamayee Maharana et al.   SCIENCE

Atomic structures of low-complexity protein segments reveal kinked β sheets that assemble networks

(2018) Michael P. Hughes et al.   SCIENCE

Protein Phase Separation: A New Phase in Cell Biology

(2018) Steven Boeynaems et al.   TRENDS IN CELL BIOLOGY

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation

(2018) Elizabeth L. Guenther et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Atomic structures of FUS LC domain segments reveal bases for reversible amyloid fibril formation

(2018) Feng Luo et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting Liquid Demixing and Stress Granule Localization

(2018) Leeanne McGurk et al.   MOLECULAR CELL

Pour Some Sugar on TDP(-43)

(2018) Steven Boeynaems et al.   MOLECULAR CELL

Poly(ADP-ribose) Engages the TDP-43 Nuclear-Localization Sequence to Regulate Granulo-Filamentous Aggregation

(2018) Leeanne McGurk et al.   BIOCHEMISTRY

TDP-43 and RNA form amyloid-like myo-granules in regenerating muscle

(2018) Thomas O. Vogler et al.   NATURE

TDP-43 extracted from frontotemporal lobar degeneration subject brains displays distinct aggregate assemblies and neurotoxic effects reflecting disease progression rates

(2018) Florent Laferrière et al.   NATURE NEUROSCIENCE

Patient-derived frontotemporal lobar degeneration brain extracts induce formation and spreading of TDP-43 pathology in vivo

(2018) Sílvia Porta et al.   Nature Communications

The Stress Granule Transcriptome Reveals Principles of mRNA Accumulation in Stress Granules

(2017) Anthony Khong et al.   MOLECULAR CELL

Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding

(2017) Bagdeser A. Ozdilek et al.   NUCLEIC ACIDS RESEARCH

Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons

(2017) Pallavi P. Gopal et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Spinal motor neuron protein supersaturation patterns are associated with inclusion body formation in ALS

(2017) Prajwal Ciryam et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation

(2017) Jacob P. Brady et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

ATP as a biological hydrotrope

(2017) Avinash Patel et al.   SCIENCE

Functional and dynamic polymerization of the ALS-linked protein TDP-43 antagonizes its pathologic aggregation

(2017) Tariq Afroz et al.   Nature Communications

Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins

(2017) Tyler S Harmon et al.   eLife

The N-terminal dimerization is required for TDP-43 splicing activity

(2017) Lei-Lei Jiang et al.   Scientific Reports

Prion-like domains as epigenetic regulators, scaffolds for subcellular organization, and drivers of neurodegenerative disease

(2016) Zachary M. March et al.   BRAIN RESEARCH

Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits

(2016) Sohini Chakrabortee et al.   CELL

ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure

(2016) Saumya Jain et al.   CELL

Compositional Control of Phase-Separated Cellular Bodies

(2016) Salman F. Banani et al.   CELL

Toxic PR Poly-Dipeptides Encoded by the C9orf72 Repeat Expansion Target LC Domain Polymers

(2016) Yi Lin et al.   CELL

A glass menagerie of low complexity sequences

(2016) Randal Halfmann   CURRENT OPINION IN STRUCTURAL BIOLOGY

Physiological functions and pathobiology of TDP-43 and FUS/TLS proteins

(2016) Antonia Ratti et al.   JOURNAL OF NEUROCHEMISTRY

Engineering therapeutic protein disaggregases

(2016) James Shorter   MOLECULAR BIOLOGY OF THE CELL

Sequence Determinants of Intracellular Phase Separation by Complex Coacervation of a Disordered Protein

(2016) Chi W. Pak et al.   MOLECULAR CELL

ALS Mutations Disrupt Phase Separation Mediated by α-Helical Structure in the TDP-43 Low-Complexity C-Terminal Domain

(2016) Alexander E. Conicella et al.   STRUCTURE

ALS-Causing Mutations Significantly Perturb the Self-Assembly and Interaction with Nucleic Acid of the Intrinsically Disordered Prion-Like Domain of TDP-43

(2016) Liangzhong Lim et al.   PLOS BIOLOGY

Phase Separation by Low Complexity Domains Promotes Stress Granule Assembly and Drives Pathological Fibrillization

(2015) Amandine Molliex et al.   CELL

A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation

(2015) Avinash Patel et al.   CELL

Liquids, Fibers, and Gels: The Many Phases of Neurodegeneration

(2015) Shana Elbaum-Garfinkle et al.   DEVELOPMENTAL CELL

Phosphorylation of C-terminal tyrosine residue 526 in FUS impairs its nuclear import

(2015) S. Darovic et al.   JOURNAL OF CELL SCIENCE

RNA Controls PolyQ Protein Phase Transitions

(2015) Huaiying Zhang et al.   MOLECULAR CELL

Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins

(2015) Yuan Lin et al.   MOLECULAR CELL

Engineering enhanced protein disaggregases for neurodegenerative disease

(2015) Meredith E Jackrel et al.   Prion

An acetylation switch controls TDP-43 function and aggregation propensity

(2015) Todd J. Cohen et al.   Nature Communications

Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)

(2015) Matthias Altmeyer et al.   Nature Communications

Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules

(2015) Sonja Kroschwald et al.   eLife

Liquid-Liquid Phase Separation in Biology

(2014) Anthony A. Hyman et al.   Annual Review of Cell and Developmental Biology

PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition

(2014) A. K. Lancaster et al.   BIOINFORMATICS

Cross-Kingdom Chemical Communication Drives a Heritable, Mutually Beneficial Prion-Based Transformation of Metabolism

(2014) Daniel F. Jarosz et al.   CELL

An Evolutionarily Conserved Prion-like Element Converts Wild Fungi from Metabolic Specialists to Generalists

(2014) Daniel F. Jarosz et al.   CELL

Potentiated Hsp104 Variants Antagonize Diverse Proteotoxic Misfolding Events

(2014) Meredith E. Jackrel et al.   CELL

Axonal Transport of TDP-43 mRNA Granules Is Impaired by ALS-Causing Mutations

(2014) Nael H. Alami et al.   NEURON

Eukaryotic Stress Granules Are Cleared by Autophagy and Cdc48/VCP Function

(2013) J. Ross Buchan et al.   CELL

Prion-like nuclear aggregation of TDP-43 during heat shock is regulated by HSP40/70 chaperones

(2013) Maria Udan-Johns et al.   HUMAN MOLECULAR GENETICS

The RNA-binding Protein Fused in Sarcoma (FUS) Functions Downstream of Poly(ADP-ribose) Polymerase (PARP) in Response to DNA Damage

(2013) Adam S. Mastrocola et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Stress granules as crucibles of ALS pathogenesis

(2013) Yun R. Li et al.   JOURNAL OF CELL BIOLOGY

Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS

(2013) Hong Joo Kim et al.   NATURE

Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis

(2013) Shuo-Chien Ling et al.   NEURON

Blessings in disguise: biological benefits of prion-like mechanisms

(2013) Gregory A. Newby et al.   TRENDS IN CELL BIOLOGY

RNA Seeds Higher-Order Assembly of FUS Protein

(2013) Jacob C. Schwartz et al.   Cell Reports

Prion-like Properties of Pathological TDP-43 Aggregates from Diseased Brains

(2013) Takashi Nonaka et al.   Cell Reports

The long non-coding RNA nuclear-enriched abundant transcript 1_2 induces paraspeckle formation in the motor neuron during the early phase of amyotrophic lateral sclerosis

(2013) Yoshinori Nishimoto et al.   Molecular Brain

The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease

(2012) Oliver D. King et al.   BRAIN RESEARCH

Cell-free Formation of RNA Granules: Bound RNAs Identify Features and Components of Cellular Assemblies

(2012) Tina W. Han et al.   CELL

Requirements for Stress Granule Recruitment of Fused in Sarcoma (FUS) and TAR DNA-binding Protein of 43 kDa (TDP-43)

(2012) Eva Bentmann et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Phase transitions in the assembly of multivalent signalling proteins

(2012) Pilong Li et al.   NATURE

Molecular Determinants and Genetic Modifiers of Aggregation and Toxicity for the ALS Disease Protein FUS/TLS

(2011) Zhihui Sun et al.   PLOS BIOLOGY

Prion-like disorders: blurring the divide between transmissibility and infectivity

(2010) M. Cushman et al.   JOURNAL OF CELL SCIENCE

Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS

(2010) Andrew C. Elden et al.   NATURE

Phosphorylation of S409/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies

(2009) Manuela Neumann et al.   ACTA NEUROPATHOLOGICA

TDP-43 Is Intrinsically Aggregation-prone, and Amyotrophic Lateral Sclerosis-linked Mutations Accelerate Aggregation and Increase Toxicity

(2009) Brian S. Johnson et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation

(2009) C. P. Brangwynne et al.   SCIENCE