{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:42:41Z","timestamp":1790073761773,"version":"4.0.1"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Disordered RNA-binding proteins and repetitive RNA sequences are the main genetic causes of several neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington\u2019s disease. Importantly, these components also seed the formation of cytoplasmic liquid-like granules, like stress granules and P bodies. Emerging evidence demonstrates that healthy granules formed via liquid-liquid phase separation can mature into solid- or gel-like inclusions that persist within the cell. These solidified inclusions are a precursor to the aggregates identified in patients, demonstrating that dysregulation of RNA granule biology is an important component of neurodegeneration. Here, we review recent literature highlighting how RNA molecules seed proteinaceous granules, the mechanisms of healthy turnover of RNA granules in cells, which biophysical properties underly a transition to solid- or gel-like material states, and why persistent granules disrupt the cellular homeostasis of neurons. We also identify various methods that will illuminate the contributions of disordered proteins and RNAs to neurodegeneration in ongoing research efforts.<\/jats:p>","DOI":"10.3389\/fmolb.2022.991641","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T07:19:35Z","timestamp":1663312775000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Aging RNA granule dynamics in neurodegeneration"],"prefix":"10.3389","volume":"9","author":[{"given":"Kevin","family":"Rhine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norah","family":"Al-Azzam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene W.","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"105585","DOI":"10.1016\/j.nbd.2021.105585","article-title":"ALS-linked cytoplasmic FUS assemblies are compositionally different from physiological stress granules and sequester hnRNPA3, a novel modifier of FUS toxicity","volume":"162","author":"An","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nrm.2017.7","article-title":"Biomolecular condensates: Organizers of cellular biochemistry","volume":"18","author":"Banani","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.cell.2017.07.010","article-title":"Elimination of toxic microsatellite repeat expansion RNA by RNA-targeting Cas9","volume":"170","author":"Batra","year":"2017","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.1038\/s41467-022-30067-3","article-title":"RNA supply drives physiological granule assembly in neurons","volume":"13","author":"Bauer","year":"2022","journal-title":"Nat. Commun."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1038\/s41592-018-0220-y","article-title":"Proximity-CLIP provides a snapshot of protein-occupied RNA elements in subcellular compartments","volume":"15","author":"Benhalevy","year":"2018","journal-title":"Nat. Methods"},{"key":"B6","doi-asserted-by":"publisher","first-page":"23079","DOI":"10.1074\/jbc.M111.328757","article-title":"Requirements for stress granule recruitment of fused in sarcoma (FUS) and TAR DNA-binding protein of 43 kDa (TDP-43)","volume":"287","author":"Bentmann","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1038\/s41596-022-00680-z","article-title":"Transcriptome-wide identification of RNA-binding protein binding sites using seCLIP-seq","volume":"17","author":"Blue","year":"2022","journal-title":"Nat. Protoc."},{"key":"B8","doi-asserted-by":"publisher","first-page":"7889","DOI":"10.1073\/pnas.1821038116","article-title":"Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties","volume":"116","author":"Boeynaems","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1016\/j.cell.2022.02.022","article-title":"Liquid-to-solid phase transition of oskar ribonucleoprotein granules is essential for their function in Drosophila embryonic development","volume":"185","author":"Bose","year":"2022","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"8678","DOI":"10.1093\/nar\/gku582","article-title":"Free mRNA in excess upon polysome dissociation is a scaffold for protein multimerization to form stress granules","volume":"42","author":"Bounedjah","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1111\/jnc.13601","article-title":"Altered mRNP granule dynamics in FTLD pathogenesis","volume":"138","author":"Bowden","year":"2016","journal-title":"J. Neurochem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1083\/jcb.200807043","article-title":"P bodies promote stress granule assembly in Saccharomyces cerevisiae","volume":"183","author":"Buchan","year":"2008","journal-title":"J. Cell Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1016\/j.molcel.2009.11.020","article-title":"Eukaryotic stress granules: The ins and outs of translation","volume":"36","author":"Buchan","year":"2009","journal-title":"Mol. Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/s41594-019-0248-4","article-title":"Cryo-EM structures of four polymorphic TDP-43 amyloid cores","volume":"26","author":"Cao","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.neuron.2012.05.029","article-title":"Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy","volume":"75","author":"Charizanis","year":"2012","journal-title":"Neuron"},{"key":"B16","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s13024-019-0310-z","article-title":"Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy","volume":"14","author":"Chew","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"B17","doi-asserted-by":"publisher","first-page":"042403","DOI":"10.1103\/PhysRevE.102.042403","article-title":"Generalized models for bond percolation transitions of associative polymers","volume":"102","author":"Choi","year":"2020","journal-title":"Phys. Rev. E"},{"key":"B18","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.molcel.2020.11.014","article-title":"Footprinting SHAPE-eCLIP reveals transcriptome-wide hydrogen bonds at RNA-protein interfaces","volume":"80","author":"Corley","year":"2020","journal-title":"Mol. Cell"},{"key":"B19","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1007\/s00401-015-1530-0","article-title":"Pur-alpha regulates cytoplasmic stress granule dynamics and ameliorates FUS toxicity","volume":"131","author":"Daigle","year":"2016","journal-title":"Acta Neuropathol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e110137","DOI":"10.15252\/embj.2021110137","article-title":"RNA is required for the integrity of multiple nuclear and cytoplasmic membrane-less RNP granules","volume":"41","author":"Decker","year":"2022","journal-title":"EMBO J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"Dejesus-Hernandez","year":"2011","journal-title":"Neuron"},{"key":"B22","doi-asserted-by":"publisher","first-page":"7189","DOI":"10.1073\/pnas.1504822112","article-title":"The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics","volume":"112","author":"Elbaum-Garfinkle","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B23","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/978-1-0716-1975-9_23","article-title":"APEX proximity labeling of stress granule proteins","volume":"2428","author":"Elmsaouri","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.neuron.2019.05.048","article-title":"Small-molecule modulation of TDP-43 recruitment to stress granules prevents persistent TDP-43 accumulation in ALS\/FTD","volume":"103","author":"Fang","year":"2019","journal-title":"Neuron"},{"key":"B25","doi-asserted-by":"publisher","first-page":"6657","DOI":"10.1021\/jacs.1c02424","article-title":"Identification of the rigid core for aged liquid droplets of an RNA-binding protein low complexity domain","volume":"143","author":"Fonda","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"B26","doi-asserted-by":"publisher","first-page":"6696","DOI":"10.1074\/jbc.RA118.005889","article-title":"Detection of TAR DNA-binding protein 43 (TDP-43) oligomers as initial intermediate species during aggregate formation","volume":"294","author":"French","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e48480","DOI":"10.7554\/eLife.48480","article-title":"RNA promotes phase separation of glycolysis enzymes into yeast G bodies in hypoxia","volume":"9","author":"Fuller","year":"2020","journal-title":"Elife"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5153","DOI":"10.1523\/JNEUROSCI.0783-09.2009","article-title":"Cross-seeding fibrillation of Q\/N-rich proteins offers new pathomechanism of polyglutamine diseases","volume":"29","author":"Furukawa","year":"2009","journal-title":"J. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1016\/j.tibs.2020.05.011","article-title":"Methods to study phase-separated condensates and the underlying molecular interactions","volume":"45","author":"Ganser","year":"2020","journal-title":"Trends biochem. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1038\/s41467-019-11241-6","article-title":"RNA is a critical element for the sizing and the composition of phase-separated RNA\u2013protein condensates","volume":"10","author":"Garcia-Jove Navarro","year":"2019","journal-title":"Nat. Commun."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1016\/j.ebiom.2015.09.053","article-title":"Stress granules modulate SYK to cause microglial cell dysfunction in alzheimer's disease","volume":"2","author":"Ghosh","year":"2015","journal-title":"EBioMedicine"},{"key":"B32","doi-asserted-by":"publisher","first-page":"5383","DOI":"10.1091\/mbc.e04-08-0715","article-title":"Stress granule assembly is mediated by prion-like aggregation of TIA-1","volume":"15","author":"Gilks","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.1038\/s41467-022-31098-6","article-title":"NUP62 localizes to ALS\/FTLD pathological assemblies and contributes to TDP-43 insolubility","volume":"13","author":"Gleixner","year":"2022","journal-title":"Nat. Commun."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3754","DOI":"10.1038\/s41598-021-83196-y","article-title":"Mechanism of karyopherin-\u03b22 binding and nuclear import of ALS variants FUS(P525L) and FUS(R495X)","volume":"11","author":"Gonzalez","year":"2021","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1126\/science.1062097","article-title":"Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils","volume":"293","author":"Gotz","year":"2001","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.cell.2020.03.049","article-title":"RNA-induced conformational switching and clustering of G3BP drive stress granule assembly by condensation","volume":"181","author":"Guillen-Boixet","year":"2020","journal-title":"Cell"},{"key":"B37","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.cell.2018.03.002","article-title":"Nuclear-import receptors reverse aberrant phase transitions of RNA-binding proteins with prion-like domains","volume":"173","author":"Guo","year":"2018","journal-title":"Cell"},{"key":"B38","doi-asserted-by":"publisher","first-page":"eabf6548","DOI":"10.1126\/science.abf6548","article-title":"Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner","volume":"372","author":"Gwon","year":"2021","journal-title":"Science"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4680","DOI":"10.1016\/j.cell.2021.07.018","article-title":"TDP-43 condensation properties specify its RNA-binding and regulatory repertoire","volume":"184","author":"Hallegger","year":"2021","journal-title":"Cell"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/s1097-2765(00)00108-8","article-title":"Regulated translation initiation controls stress-induced gene expression in mammalian cells","volume":"6","author":"Harding","year":"2000","journal-title":"Mol. Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e30294","DOI":"10.7554\/eLife.30294","article-title":"Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins","volume":"6","author":"Harmon","year":"2017","journal-title":"Elife"},{"key":"B42","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1016\/j.cell.2018.03.004","article-title":"Phase separation of FUS is suppressed by its nuclear import receptor and arginine methylation","volume":"173","author":"Hofweber","year":"2018","journal-title":"Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/s41586-019-1502-y","article-title":"DEAD-box ATPases are global regulators of phase-separated organelles","volume":"573","author":"Hondele","year":"2019","journal-title":"Nature"},{"key":"B44","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.molcel.2017.09.030","article-title":"The dynamics of mRNA turnover revealed by single-molecule imaging in single cells","volume":"68","author":"Horvathova","year":"2017","journal-title":"Mol. Cell"},{"key":"B45","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.semcdb.2019.05.020","article-title":"Nucleocytoplasmic transport defects in neurodegeneration - cause or consequence?","volume":"99","author":"Hutten","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"B46","first-page":"490956","article-title":"Fixation can change the appearance of phase separation in living cells","volume":"2005","author":"Irgen-Gioro","year":"2022","journal-title":"bioRxiv"},{"key":"B47","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.cell.2020.04.009","article-title":"Condensation of Ded1p promotes a translational switch from housekeeping to stress protein production","volume":"181","author":"Iserman","year":"2020","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1101\/gad.17838411","article-title":"Stress puts TIA on TOP","volume":"25","author":"Ivanov","year":"2011","journal-title":"Genes Dev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nature22386","article-title":"RNA phase transitions in repeat expansion disorders","volume":"546","author":"Jain","year":"2017","journal-title":"Nature"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1126\/science.aaw4951","article-title":"Protein condensates as aging Maxwell fluids","volume":"370","author":"Jawerth","year":"2020","journal-title":"Science"},{"key":"B51","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.celrep.2017.06.082","article-title":"Glycolytic enzymes coalesce in G bodies under hypoxic stress","volume":"20","author":"Jin","year":"2017","journal-title":"Cell Rep."},{"key":"B52","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.cell.2012.04.017","article-title":"Cell-free formation of RNA granules: Low complexity sequence domains form dynamic fibers within hydrogels","volume":"149","author":"Kato","year":"2012","journal-title":"Cell"},{"key":"B53","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.molcel.2017.10.015","article-title":"The stress granule transcriptome reveals principles of mRNA accumulation in stress granules","volume":"68","author":"Khong","year":"2017","journal-title":"Mol. Cell"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1091\/mbc.E15-12-0844","article-title":"An improved smaller biotin ligase for BioID proximity labeling","volume":"27","author":"Kim","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/nature11922","article-title":"Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS","volume":"495","author":"Kim","year":"2013","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.tibs.2013.05.003","article-title":"Huntington's disease: Underlying molecular mechanisms and emerging concepts","volume":"38","author":"Labbadia","year":"2013","journal-title":"Trends biochem. Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"104105","DOI":"10.1016\/j.isci.2022.104105","article-title":"RNA chain length and stoichiometry govern surface tension and stability of protein-RNA condensates","volume":"25","author":"Laghmach","year":"2022","journal-title":"iScience"},{"key":"B58","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1038\/s41556-022-00933-9","article-title":"Illuminating RNA biology through imaging","volume":"24","author":"Le","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e52896","DOI":"10.7554\/eLife.52896","article-title":"Recruitment of mRNAs to P granules by condensation with intrinsically-disordered proteins","volume":"9","author":"Lee","year":"2020","journal-title":"Elife"},{"key":"B60","doi-asserted-by":"publisher","first-page":"4221","DOI":"10.1073\/pnas.1117019109","article-title":"RNase H-mediated degradation of toxic RNA in myotonic dystrophy type 1","volume":"109","author":"Lee","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B61","doi-asserted-by":"publisher","first-page":"e17056","DOI":"10.7554\/eLife.17056","article-title":"Real-time imaging of Huntingtin aggregates diverting target search and gene transcription","volume":"5","author":"Li","year":"2016","journal-title":"Elife"},{"key":"B62","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.devcel.2015.02.002","article-title":"Neuronal aggregates: Formation, clearance, and spreading","volume":"32","author":"Lim","year":"2015","journal-title":"Dev. Cell"},{"key":"B63","doi-asserted-by":"publisher","first-page":"3030","DOI":"10.1038\/s41467-022-30521-2","article-title":"Dynamic arrest and aging of biomolecular condensates are modulated by low-complexity domains, RNA and biochemical activity","volume":"13","author":"Linsenmeier","year":"2022","journal-title":"Nat. Commun."},{"key":"B64","doi-asserted-by":"publisher","first-page":"e13250","DOI":"10.1371\/journal.pone.0013250","article-title":"Tar DNA binding protein-43 (TDP-43) associates with stress granules: Analysis of cultured cells and pathological brain tissue","volume":"5","author":"Liu-Yesucevitz","year":"2010","journal-title":"PLoS One"},{"key":"B65","first-page":"464447","article-title":"Heat shock chaperone HSPB1 regulates cytoplasmic TDP-43 phase separation and liquid-to-gel transition","volume":"2010","author":"Lu","year":"2021","journal-title":"bioRxiv"},{"key":"B66","doi-asserted-by":"publisher","first-page":"4716","DOI":"10.1021\/jacs.1c12085","article-title":"Nucleobase clustering contributes to the formation and hollowing of repeat-expansion RNA condensate","volume":"144","author":"Ma","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"B67","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1126\/science.aar7366","article-title":"RNA buffers the phase separation behavior of prion-like RNA binding proteins","volume":"360","author":"Maharana","year":"2018","journal-title":"Science"},{"key":"B68","first-page":"461736","article-title":"RNA helicase DDX6 in P-bodies is essential for the assembly of stress granules","volume":"2009","author":"Majerciak","year":"2021","journal-title":"bioRxiv"},{"key":"B69","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.neuron.2019.01.048","article-title":"RNA binding antagonizes neurotoxic phase transitions of TDP-43","volume":"102","author":"Mann","year":"2019","journal-title":"Neuron"},{"key":"B70","doi-asserted-by":"publisher","first-page":"109685","DOI":"10.1016\/j.celrep.2021.109685","article-title":"Persistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress","volume":"36","author":"Markmiller","year":"2021","journal-title":"Cell Rep."},{"key":"B71","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.cell.2017.12.032","article-title":"Context-dependent and disease-specific diversity in protein interactions within stress granules","volume":"172","author":"Markmiller","year":"2018","journal-title":"Cell"},{"key":"B72","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.molcel.2020.10.032","article-title":"Spatiotemporal proteomic analysis of stress granule disassembly using APEX reveals regulation by SUMOylation and links to ALS pathogenesis","volume":"80","author":"Marmor-Kollet","year":"2020","journal-title":"Mol. Cell"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1016\/j.cell.2020.11.010","article-title":"Single-molecule imaging reveals translation of mRNAs localized to stress granules","volume":"183","author":"Mateju","year":"2020","journal-title":"Cell"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.15252\/embj.201695957","article-title":"An aberrant phase transition of stress granules triggered by misfolded protein and prevented by chaperone function","volume":"36","author":"Mateju","year":"2017","journal-title":"EMBO J."},{"key":"B75","doi-asserted-by":"publisher","first-page":"e00313-19","DOI":"10.1128\/MCB.00313-19","article-title":"Transcriptome-Wide comparison of stress granules and P-bodies reveals that translation plays a major role in RNA partitioning","volume":"39","author":"Matheny","year":"2019","journal-title":"Mol. Cell. Biol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1126\/science.abb8032","article-title":"Beyond aggregation: Pathological phase transitions in neurodegenerative disease","volume":"370","author":"Mathieu","year":"2020","journal-title":"Science"},{"key":"B77","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/jnc.14541","article-title":"Machado-joseph disease\/spinocerebellar ataxia type 3: Lessons from disease pathogenesis and clues into therapy","volume":"148","author":"Matos","year":"2019","journal-title":"J. Neurochem."},{"key":"B78","doi-asserted-by":"publisher","first-page":"eabc3593","DOI":"10.1126\/science.abc3593","article-title":"Ubiquitination is essential for recovery of cellular activities after heat shock","volume":"372","author":"Maxwell","year":"2021","journal-title":"Science"},{"key":"B79","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1016\/j.molcel.2022.05.018","article-title":"A conceptual framework for understanding phase separation and addressing open questions and challenges","volume":"82","author":"Mittag","year":"2022","journal-title":"Mol. Cell"},{"key":"B80","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.cell.2015.09.015","article-title":"Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization","volume":"163","author":"Molliex","year":"2015","journal-title":"Cell"},{"key":"B81","doi-asserted-by":"publisher","first-page":"e202004120","DOI":"10.1083\/jcb.202004120","article-title":"Coupling of translation quality control and mRNA targeting to stress granules","volume":"219","author":"Moon","year":"2020","journal-title":"J. Cell Biol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.cell.2017.08.048","article-title":"Structure of FUS protein fibrils and its relevance to self-assembly and phase separation of low-complexity domains","volume":"171","author":"Murray","year":"2017","journal-title":"Cell"},{"key":"B83","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.molcel.2019.09.022","article-title":"Loss of dynamic RNA interaction and aberrant phase separation induced by two distinct types of ALS\/FTD-Linked FUS mutations","volume":"77","author":"Niaki","year":"2020","journal-title":"Mol. Cell"},{"key":"B84","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/S1046-2023(02)00021-X","article-title":"Reversible cross-linking combined with immunoprecipitation to study RNA-protein interactions in vivo","volume":"26","author":"Niranjanakumari","year":"2002","journal-title":"Methods"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1074\/jbc.M113.516492","article-title":"Intranuclear aggregation of mutant FUS\/TLS as a molecular pathomechanism of amyotrophic lateral sclerosis","volume":"289","author":"Nomura","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B86","doi-asserted-by":"publisher","first-page":"167220","DOI":"10.1016\/j.jmb.2021.167220","article-title":"Nuclear-import receptors counter deleterious phase transitions in neurodegenerative disease","volume":"434","author":"Odeh","year":"2022","journal-title":"J. Mol. Biol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.molcel.2019.07.030","article-title":"Proximity RNA labeling by APEX-seq reveals the organization of translation initiation complexes and repressive RNA granules","volume":"75","author":"Padron","year":"2019","journal-title":"Mol. Cell"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.cell.2015.07.047","article-title":"A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation","volume":"162","author":"Patel","year":"2015","journal-title":"Cell"},{"key":"B89","doi-asserted-by":"publisher","first-page":"2782","DOI":"10.1038\/s41467-022-30066-4","article-title":"RNP components condense into repressive RNP granules in the aging brain","volume":"13","author":"Pushpalatha","year":"2022","journal-title":"Nat. Commun."},{"key":"B90","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/s41557-020-0465-9","article-title":"\u03b1-Synuclein aggregation nucleates through liquid\u2013liquid phase separation","volume":"12","author":"Ray","year":"2020","journal-title":"Nat. Chem."},{"key":"B91","doi-asserted-by":"publisher","first-page":"7713","DOI":"10.1093\/nar\/gkab582","article-title":"The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation","volume":"49","author":"Reber","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B92","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.bcp.2018.10.009","article-title":"Differences between acute and chronic stress granules, and how these differences may impact function in human disease","volume":"162","author":"Reineke","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.molcel.2022.01.018","article-title":"Poly(ADP-ribose) drives condensation of FUS via a transient interaction","volume":"82","author":"Rhine","year":"","journal-title":"Mol. Cell"},{"key":"B94","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.molcel.2020.10.014","article-title":"ALS\/FTLD-Linked mutations in FUS Glycine residues cause accelerated gelation and reduced interactions with wild-type FUS","volume":"80","author":"Rhine","year":"","journal-title":"Mol. Cell"},{"key":"B95","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.ymeth.2021.02.012","article-title":"Single-molecule and ensemble methods to probe RNP nucleation and condensate properties","volume":"197","author":"Rhine","year":"","journal-title":"Methods"},{"key":"B96","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1146\/annurev-biophys-052118-115508","article-title":"RNA droplets","volume":"49","author":"Rhine","year":"","journal-title":"Annu. Rev. Biophys."},{"key":"B97","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1126\/science.1141736","article-title":"Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model","volume":"316","author":"Roberson","year":"2007","journal-title":"Science"},{"key":"B98","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41580-020-0264-6","article-title":"RNA contributions to the form and function of biomolecular condensates","volume":"22","author":"Roden","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1083\/jcb.201112098","article-title":"A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells","volume":"196","author":"Roux","year":"2012","journal-title":"J. Cell Biol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"2822","DOI":"10.1016\/j.neurobiolaging.2014.07.026","article-title":"Autophagy regulates amyotrophic lateral sclerosis-linked fused in sarcoma-positive stress granules in neurons","volume":"35","author":"Ryu","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"B101","doi-asserted-by":"publisher","first-page":"e1009810","DOI":"10.1371\/journal.pcbi.1009810","article-title":"RNA length has a non-trivial effect in the stability of biomolecular condensates formed by RNA-binding proteins","volume":"18","author":"Sanchez-Burgos","year":"2022","journal-title":"PLoS Comput. Biol."},{"key":"B102","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1016\/j.celrep.2013.11.017","article-title":"RNA seeds higher-order assembly of FUS protein","volume":"5","author":"Schwartz","year":"2013","journal-title":"Cell Rep."},{"key":"B103","doi-asserted-by":"publisher","first-page":"2588","DOI":"10.1016\/j.molcel.2022.04.022","article-title":"Sexually dimorphic RNA helicases DDX3X and DDX3Y differentially regulate RNA metabolism through phase separation","volume":"82","author":"Shen","year":"","journal-title":"Mol. Cell"},{"key":"B104","doi-asserted-by":"publisher","first-page":"503964","DOI":"10.1101\/2022.08.15.503964","article-title":"Solid\/liquid coexistence during aging of FUS condensates","volume":"2008","author":"Shen","year":"","journal-title":"bioRxiv"},{"key":"B105","doi-asserted-by":"publisher","first-page":"3655","DOI":"10.1016\/j.celrep.2020.02.078","article-title":"Mice carrying ALS mutant TDP-43, but not mutant FUS, display in vivo defects in axonal transport of signaling endosomes","volume":"30","author":"Sleigh","year":"2020","journal-title":"Cell Rep."},{"key":"B106","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1126\/science.1154584","article-title":"TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis","volume":"319","author":"Sreedharan","year":"2008","journal-title":"Science"},{"key":"B107","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/j.cell.2013.07.031","article-title":"Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells","volume":"154","author":"Thedieck","year":"2013","journal-title":"Cell"},{"key":"B108","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1083\/jcb.200212128","article-title":"The RasGAP-associated endoribonuclease G3BP assembles stress granules","volume":"160","author":"Tourriere","year":"2003","journal-title":"J. Cell Biol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.molcel.2020.05.008","article-title":"Sequence-independent self-assembly of germ granule mRNAs into homotypic clusters","volume":"78","author":"Trcek","year":"2020","journal-title":"Mol. Cell"},{"key":"B110","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s004010100364","article-title":"Non-expanded polyglutamine proteins in intranuclear inclusions of hereditary ataxias \u2013 triple-labeling immunofluorescence study","volume":"102","author":"Uchihara","year":"2001","journal-title":"Acta Neuropathol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/nmeth.3810","article-title":"Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP)","volume":"13","author":"Van Nostrand","year":"2016","journal-title":"Nat. Methods"},{"key":"B112","doi-asserted-by":"publisher","first-page":"2734","DOI":"10.1073\/pnas.1800038115","article-title":"RNA self-assembly contributes to stress granule formation and defining the stress granule transcriptome","volume":"115","author":"Van Treeck","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B113","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1126\/science.1165942","article-title":"Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6","volume":"323","author":"Vance","year":"2009","journal-title":"Science"},{"key":"B114","doi-asserted-by":"publisher","first-page":"8270","DOI":"10.1523\/JNEUROSCI.1592-12.2012","article-title":"Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopathies","volume":"32","author":"Vanderweyde","year":"2012","journal-title":"J. Neurosci."},{"key":"B115","doi-asserted-by":"publisher","first-page":"e98049","DOI":"10.15252\/embj.201798049","article-title":"Tau protein liquid-liquid phase separation can initiate tau aggregation","volume":"37","author":"Wegmann","year":"2018","journal-title":"EMBO J."},{"key":"B116","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev-biochem-032620-105429","article-title":"The role of DEAD-box ATPases in gene expression and the regulation of RNA-protein condensates","volume":"91","author":"Weis","year":"2022","journal-title":"Annu. Rev. Biochem."},{"key":"B117","doi-asserted-by":"publisher","first-page":"e18413","DOI":"10.7554\/eLife.18413","article-title":"Distinct stages in stress granule assembly and disassembly","volume":"5","author":"Wheeler","year":"2016","journal-title":"Elife"},{"key":"B118","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1038\/s41467-022-30158-1","article-title":"Characterization of RNA content in individual phase-separated coacervate microdroplets","volume":"13","author":"Wollny","year":"2022","journal-title":"Nat. Commun."},{"key":"B119","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41583-019-0222-5","article-title":"Stress granules and neurodegeneration","volume":"20","author":"Wolozin","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"B120","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.cell.2020.03.046","article-title":"G3BP1 is a tunable switch that triggers phase separation to assemble stress granules","volume":"181","author":"Yang","year":"2020","journal-title":"Cell"},{"key":"B121","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2018.03.003","article-title":"Nuclear import receptor inhibits phase separation of FUS through binding to multiple sites","volume":"173","author":"Yoshizawa","year":"2018","journal-title":"Cell"},{"key":"B122","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.molcel.2017.12.020","article-title":"High-density proximity mapping reveals the subcellular organization of mRNA-associated granules and bodies","volume":"69","author":"Youn","year":"2018","journal-title":"Mol. Cell"},{"key":"B123","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1016\/j.jmb.2019.01.028","article-title":"RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43","volume":"431","author":"Zacco","year":"2019","journal-title":"J. Mol. Biol."},{"key":"B124","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1016\/j.cell.2018.03.025","article-title":"Stress granule assembly disrupts nucleocytoplasmic transport","volume":"173","author":"Zhang","year":"2018","journal-title":"Cell"},{"key":"B125","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature14973","article-title":"The C9orf72 repeat expansion disrupts nucleocytoplasmic transport","volume":"525","author":"Zhang","year":"2015","journal-title":"Nature"},{"key":"B126","doi-asserted-by":"publisher","first-page":"e39578","DOI":"10.7554\/eLife.39578","article-title":"Chronic optogenetic induction of stress granules is cytotoxic and reveals the evolution of ALS-FTD pathology","volume":"8","author":"Zhang","year":"2019","journal-title":"Elife"},{"key":"B127","doi-asserted-by":"publisher","first-page":"6863","DOI":"10.1093\/hmg\/ddu409","article-title":"An ALS-mutant TDP-43 neurotoxic peptide adopts an anti-parallel beta-structure and induces TDP-43 redistribution","volume":"23","author":"Zhu","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B128","doi-asserted-by":"publisher","first-page":"e19727","DOI":"10.1371\/journal.pone.0019727","article-title":"Characterizing mRNA interactions with RNA granules during translation initiation inhibition","volume":"6","author":"Zurla","year":"2011","journal-title":"PLoS One"}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2022.991641\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T07:19:49Z","timestamp":1663312789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2022.991641\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,16]]},"references-count":128,"alternative-id":["10.3389\/fmolb.2022.991641"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2022.991641","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,16]]},"article-number":"991641"}}