{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:16:43Z","timestamp":1792149403896,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011251","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000}}],"reference-count":118,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["15\/IA\/3123"],"award-info":[{"award-number":["15\/IA\/3123"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206405\/Z\/17\/Z"],"award-info":[{"award-number":["206405\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009053","name":"The Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","award":["IA\/I\/19\/1\/504286"],"award-info":[{"award-number":["IA\/I\/19\/1\/504286"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005879","name":"National Centre for Biological Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005879","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Government of India","award":["JC Bose Fellowship"],"award-info":[{"award-number":["JC Bose Fellowship"]}]},{"name":"Science and Engineering Research Board-VAJARA","award":["VJR\/2017\/000284"],"award-info":[{"award-number":["VJR\/2017\/000284"]}]},{"DOI":"10.13039\/501100001596","name":"Irish Research Council for Science, Engineering and Technology","doi-asserted-by":"publisher","award":["GOIPG\/2018\/1947"],"award-info":[{"award-number":["GOIPG\/2018\/1947"]}],"id":[{"id":"10.13039\/501100001596","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008605","name":"Indian National Science Academy","doi-asserted-by":"publisher","award":["INSA\/SP\/YSP\/143\/2017"],"award-info":[{"award-number":["INSA\/SP\/YSP\/143\/2017"]}],"id":[{"id":"10.13039\/100008605","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DST INSPIRE","award":["DST\/AORC-IF\/UPGRD\/IF180265"],"award-info":[{"award-number":["DST\/AORC-IF\/UPGRD\/IF180265"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Ataxin-2 (\n                    <jats:italic>ATXN2<\/jats:italic>\n                    ) is a gene implicated in spinocerebellar ataxia type II (SCA2), amyotrophic lateral sclerosis (ALS) and Parkinsonism. The encoded protein is a therapeutic target for ALS and related conditions. ATXN2 (or Atx2 in insects) can function in translational activation, translational repression, mRNA stability and in the assembly of mRNP-granules, a process mediated by intrinsically disordered regions (IDRs). Previous work has shown that the LSm (Like-Sm) domain of Atx2, which can help stimulate mRNA translation, antagonizes mRNP-granule assembly. Here we advance these findings through a series of experiments on\n                    <jats:italic>Drosophila<\/jats:italic>\n                    and human Ataxin-2 proteins. Results of Targets of RNA Binding Proteins Identified by Editing (TRIBE), co-localization and immunoprecipitation experiments indicate that a polyA-binding protein (PABP) interacting, PAM2 motif of Ataxin-2 may be a major determinant of the mRNA and protein content of Ataxin-2 mRNP granules. Experiments with transgenic\n                    <jats:italic>Drosophila<\/jats:italic>\n                    indicate that while the Atx2-LSm domain may protect against neurodegeneration, structured PAM2- and unstructured IDR- interactions both support Atx2-induced cytotoxicity. Taken together, the data lead to a proposal for how Ataxin-2 interactions are remodelled during translational control and how structured and non-structured interactions contribute differently to the specificity and efficiency of RNP granule condensation as well as to neurodegeneration.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1011251","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T13:48:54Z","timestamp":1716212934000},"page":"e1011251","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Structured and disordered regions of Ataxin-2 contribute differently to the specificity and efficiency of mRNP granule formation"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-582X","authenticated-orcid":true,"given":"Arnas","family":"Petrauskas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6339-1905","authenticated-orcid":true,"given":"Daniel L.","family":"Fortunati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4020-1769","authenticated-orcid":true,"given":"Arvind Reddy","family":"Kandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9184-6006","authenticated-orcid":true,"given":"Sai Shruti","family":"Pothapragada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9159-8615","authenticated-orcid":true,"given":"Khushboo","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9793-0404","authenticated-orcid":true,"given":"Amanjot","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9209-5251","authenticated-orcid":true,"given":"Joern","family":"Huelsmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Hillebrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3957-1236","authenticated-orcid":true,"given":"Dhananjay","family":"Chaturvedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongbo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-9272","authenticated-orcid":true,"given":"Chunghun","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-2701","authenticated-orcid":true,"given":"Georg","family":"Auburger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"VijayRaghavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mani","family":"Ramaswami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5114-3429","authenticated-orcid":true,"given":"Baskar","family":"Bakthavachalu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"pgen.1011251.ref001","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.4161\/15476286.2014.972208","article-title":"mRNP granules: Assembly, function, and connections with disease","volume":"11","author":"JR Buchan","year":"2014","journal-title":"RNA Biol"},{"key":"pgen.1011251.ref002","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/tra.12672","article-title":"Neuronal ribonucleoprotein granules: Dynamic sensors of localized signals","volume":"20","author":"N Formicola","year":"2019","journal-title":"Traffic"},{"key":"pgen.1011251.ref003","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.neuron.2006.08.021","article-title":"Neuronal RNA Granules: Movers and Makers","volume":"51","author":"MA Kiebler","year":"2006","journal-title":"Neuron"},{"key":"pgen.1011251.ref004","doi-asserted-by":"crossref","first-page":"7812","DOI":"10.1523\/JNEUROSCI.16-24-07812.1996","article-title":"Translocation of RNA granules in living neurons","volume":"16","author":"RB Knowles","year":"1996","journal-title":"J Neurosci"},{"key":"pgen.1011251.ref005","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.cell.2009.01.044","article-title":"mRNA localization: gene expression in the spatial dimension","volume":"136","author":"KC Martin","year":"2009","journal-title":"Cell"},{"key":"pgen.1011251.ref006","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1261\/rna.078999.121","article-title":"RNA multimerization as an organizing force for liquid-liquid phase separation","volume":"28","author":"PC Bevilacqua","year":"2022","journal-title":"RNA"},{"key":"pgen.1011251.ref007","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1261\/rna.078204.120","article-title":"RNA partitioning into stress granules is based on the summation of multiple interactions","volume":"27","author":"T Matheny","year":"2020","journal-title":"RNA"},{"key":"pgen.1011251.ref008","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.cell.2018.07.023","article-title":"Emerging Roles for Intermolecular RNA-RNA Interactions in RNP Assemblies","volume":"174","author":"B Van Treeck","year":"2018","journal-title":"Cell"},{"key":"pgen.1011251.ref009","doi-asserted-by":"crossref","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":"B Van Treeck","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1011251.ref010","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1083\/jcb.147.7.1431","article-title":"RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules","volume":"147","author":"NL Kedersha","year":"1999","journal-title":"J Cell Biol"},{"key":"pgen.1011251.ref011","doi-asserted-by":"crossref","first-page":"a032813","DOI":"10.1101\/cshperspect.a032813","article-title":"Stress Granules and Processing Bodies in Translational Control.","volume":"11","author":"P Ivanov","year":"2019","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"pgen.1011251.ref012","first-page":"61","article-title":"Mammalian Stress Granules and Processing Bodies.","volume-title":"Methods in Enzymology","author":"N Kedersha","year":"2007"},{"key":"pgen.1011251.ref013","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.molcel.2019.09.014","article-title":"Properties of Stress Granule and P-Body Proteomes","volume":"76","author":"J-Y Youn","year":"2019","journal-title":"Mol Cell"},{"key":"pgen.1011251.ref014","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1126\/science.aaa3650","article-title":"Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways","volume":"347","author":"ET Cirulli","year":"2015","journal-title":"Science (80-)."},{"key":"pgen.1011251.ref015","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1093\/hmg\/dds116","article-title":"Evaluating the role of the FUS\/TLS-related gene EWSR1 in amyotrophic lateral sclerosis","volume":"21","author":"J Couthouis","year":"2012","journal-title":"Hum Mol Genet"},{"key":"pgen.1011251.ref016","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature09320","article-title":"Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS","volume":"466","author":"AC Elden","year":"2010","journal-title":"Nature"},{"key":"pgen.1011251.ref017","doi-asserted-by":"crossref","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":"HJ Kim","year":"2013","journal-title":"Nature"},{"key":"pgen.1011251.ref018","first-page":"10: 509","article-title":"RNA metabolism in neurodegenerative disease.","author":"EY Liu","year":"2017","journal-title":"Dis Model & Mech."},{"key":"pgen.1011251.ref019","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature20413","article-title":"Decoding ALS: from genes to mechanism","volume":"539","author":"JP Taylor","year":"2016","journal-title":"Nature"},{"key":"pgen.1011251.ref020","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41583-019-0222-5","article-title":"Stress granules and neurodegeneration.","volume":"20","author":"B Wolozin","year":"2019","journal-title":"Nat Rev Neurosci"},{"key":"pgen.1011251.ref021","doi-asserted-by":"crossref","first-page":"e13136","DOI":"10.1111\/acel.13136","article-title":"The involvement of stress granules in aging and aging-associated diseases","volume":"19","author":"X Cao","year":"2020","journal-title":"Aging Cell"},{"key":"pgen.1011251.ref022","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1083\/jcb.201302044","article-title":"Stress granules as crucibles of ALS pathogenesis","volume":"201","author":"YR Li","year":"2013","journal-title":"J Cell Biol"},{"key":"pgen.1011251.ref023","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev-cellbio-040320-120625","article-title":"Developing Therapies for Neurodegenerative Disorders: Insights from Protein Aggregation and Cellular Stress Responses","volume":"36","author":"GR Mallucci","year":"2020","journal-title":"Annu Rev Cell Dev Biol"},{"key":"pgen.1011251.ref024","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.tcb.2016.05.004","article-title":"Principles and Properties of Stress Granules","volume":"26","author":"DSW Protter","year":"2016","journal-title":"Trends Cell Biol"},{"key":"pgen.1011251.ref025","doi-asserted-by":"crossref","first-page":"105143","DOI":"10.1016\/j.phrs.2020.105143","article-title":"Targeting stress granules: A novel therapeutic strategy for human diseases","volume":"161","author":"F Wang","year":"2020","journal-title":"Pharmacol Res"},{"key":"pgen.1011251.ref026","doi-asserted-by":"crossref","first-page":"e18413","DOI":"10.7554\/eLife.18413","article-title":"Distinct stages in stress granule assembly and disassembly.","volume":"5","author":"JR Wheeler","year":"2016","journal-title":"Elife."},{"key":"pgen.1011251.ref027","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1261\/rna.073601.119","article-title":"The landscape of eukaryotic mRNPs","volume":"26","author":"A Khong","year":"2020","journal-title":"RNA"},{"key":"pgen.1011251.ref028","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.neuron.2019.07.004","article-title":"Inhibition of Axon Regeneration by Liquid-like TIAR-2","volume":"104","author":"MG Andrusiak","year":"2019","journal-title":"Granules. Neuron"},{"key":"pgen.1011251.ref029","first-page":"118","article-title":"TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau","author":"PEA Ash","year":"2021","journal-title":"Proc Natl Acad Sci"},{"key":"pgen.1011251.ref030","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.tibs.2015.08.012","article-title":"Emerging Roles of Disordered Sequences in RNA-Binding Proteins","volume":"40","author":"S Calabretta","year":"2015","journal-title":"Trends Biochem Sci"},{"key":"pgen.1011251.ref031","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1083\/jcb.200704147","article-title":"Edc3p and a glutamine\/asparagine-rich domain of Lsm4p function in processing body assembly in Saccharomyces cerevisiae","volume":"179","author":"CJ Decker","year":"2007","journal-title":"J Cell Biol"},{"key":"pgen.1011251.ref032","doi-asserted-by":"crossref","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":"N Gilks","year":"2004","journal-title":"Mol Biol Cell"},{"key":"pgen.1011251.ref033","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12964-016-0132-3","article-title":"The new (dis)order in RNA regulation.","volume":"14","author":"AI J\u00e4rvelin","year":"2016","journal-title":"Cell Commun Signal"},{"key":"pgen.1011251.ref034","first-page":"118","article-title":"Interaction hot spots for phase separation revealed by NMR studies of a CAPRIN1 condensed phase","author":"TH Kim","year":"2021","journal-title":"Proc Natl Acad Sci"},{"key":"pgen.1011251.ref035","doi-asserted-by":"crossref","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":"P Yang","year":"2020","journal-title":"Cell"},{"key":"pgen.1011251.ref036","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.jmb.2020.03.004","article-title":"Liquid-Liquid Phase Separation and Its Mechanistic Role in Pathological Protein Aggregation","volume":"432","author":"WM Babinchak","year":"2020","journal-title":"J Mol Biol"},{"key":"pgen.1011251.ref037","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.cell.2012.04.016","article-title":"Cell-free formation of RNA granules: Bound RNAs identify features and components of cellular assemblies","volume":"149","author":"TW Han","year":"2012","journal-title":"Cell"},{"key":"pgen.1011251.ref038","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev-cellbio-100913-013325","article-title":"Liquid-Liquid Phase Separation in Biology","volume":"30","author":"AA Hyman","year":"2014","journal-title":"Annu Rev Cell Dev Biol"},{"key":"pgen.1011251.ref039","doi-asserted-by":"crossref","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":"M Kato","year":"2012","journal-title":"Cell"},{"key":"pgen.1011251.ref040","doi-asserted-by":"crossref","first-page":"19110","DOI":"10.1074\/jbc.M117.800466","article-title":"Intrinsically disordered sequences enable modulation of protein phase separation through distributed tyrosine motifs","volume":"292","author":"Y Lin","year":"2017","journal-title":"J Biol Chem"},{"key":"pgen.1011251.ref041","doi-asserted-by":"crossref","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":"DT Murray","year":"2017","journal-title":"Cell"},{"key":"pgen.1011251.ref042","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/s41594-019-0250-x","article-title":"Molecular interactions underlying liquid\u2212liquid phase separation of the FUS low-complexity domain","volume":"26","author":"AC Murthy","year":"2019","journal-title":"Nat Struct & Mol Biol."},{"key":"pgen.1011251.ref043","first-page":"357","article-title":"Liquid phase condensation in cell physiology and disease","author":"Y Shin","year":"2017","journal-title":"Science"},{"key":"pgen.1011251.ref044","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1073\/pnas.79.5.1558","article-title":"Immunofluorescence visualization of germ-line-specific cytoplasmic granules in embryos, larvae, and adults of Caenorhabditis elegans","volume":"79","author":"S Strome","year":"1982","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1011251.ref045","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1083\/jcb.201404124","article-title":"Assemblages: Functional units formed by cellular phase separation","volume":"206","author":"JA Toretsky","year":"2014","journal-title":"J Cell Biol"},{"key":"pgen.1011251.ref046","doi-asserted-by":"crossref","first-page":"6696","DOI":"10.1074\/jbc.R115.695056","article-title":"Modulation of Intrinsically Disordered Protein Function by Post-translational Modifications","volume":"291","author":"A Bah","year":"2016","journal-title":"J Biol Chem"},{"key":"pgen.1011251.ref047","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature13999","article-title":"Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch","volume":"519","author":"A Bah","year":"2014","journal-title":"Nature"},{"key":"pgen.1011251.ref048","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1016\/j.febslet.2015.06.003","article-title":"Functional advantages of dynamic protein disorder","volume":"589","author":"RB Berlow","year":"2015","journal-title":"FEBS Lett"},{"key":"pgen.1011251.ref049","doi-asserted-by":"crossref","first-page":"7137","DOI":"10.1074\/jbc.TM118.001189","article-title":"Friend or foe\u2014Post-translational modifications as regulators of phase separation and RNP granule dynamics","volume":"294","author":"M Hofweber","year":"2019","journal-title":"J Biol Chem"},{"key":"pgen.1011251.ref050","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.cell.2013.10.033","article-title":"Phosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains","volume":"155","author":"I Kwon","year":"2013","journal-title":"Cell"},{"key":"pgen.1011251.ref051","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.celrep.2017.12.036","article-title":"TIA-1 Self-Multimerization, Phase Separation, and Recruitment into Stress Granules Are Dynamically Regulated by Zn2+","volume":"22","author":"JB Rayman","year":"2018","journal-title":"Cell Rep"},{"key":"pgen.1011251.ref052","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41589-018-0180-7","article-title":"Acetylation of intrinsically disordered regions regulates phase separation","volume":"15","author":"M Saito","year":"2018","journal-title":"Nat Chem Biol"},{"key":"pgen.1011251.ref053","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cell.2018.12.035","article-title":"Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates","volume":"176","author":"S Alberti","year":"2019","journal-title":"Cell"},{"key":"pgen.1011251.ref054","doi-asserted-by":"crossref","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":"A Patel","year":"2015","journal-title":"Cell"},{"key":"pgen.1011251.ref055","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.cell.2013.07.038","article-title":"Review Altered Ribostasis: RNA-Protein Granules in Degenerative Disorders","volume":"154","author":"M Ramaswami","year":"2013","journal-title":"Cell"},{"key":"pgen.1011251.ref056","first-page":"114","article-title":"Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury","author":"A Chou","year":"2017","journal-title":"Proc Natl Acad Sci"},{"key":"pgen.1011251.ref057","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1093\/brain\/awx074","article-title":"Repurposed drugs targeting eIF2&alpha;-P-mediated translational repression prevent neurodegeneration in mice.","volume":"140","author":"M Halliday","year":"2017","journal-title":"Brain."},{"key":"pgen.1011251.ref058","first-page":"2015","article-title":"The small molecule ISRIB reverses the effects of eIF2\u03b1 phosphorylation on translation and stress granule assembly.","author":"C Sidrauski","year":"2015","journal-title":"Elife"},{"key":"pgen.1011251.ref059","first-page":"7","article-title":"The small molecule ISRIB rescues the stability and activity of Vanishing White Matter Disease eIF2B mutant complexes.","author":"YL Wong","year":"2018","journal-title":"Elife"},{"key":"pgen.1011251.ref060","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.molcel.2020.10.031","article-title":"ISRIB Blunts the Integrated Stress Response by Allosterically Antagonising the Inhibitory Effect of Phosphorylated eIF2 on eIF2B","volume":"81","author":"AF Zyryanova","year":"2021","journal-title":"Mol Cell"},{"key":"pgen.1011251.ref061","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.neuron.2018.04.032","article-title":"RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration","volume":"98","author":"B Bakthavachalu","year":"2018","journal-title":"Neuron"},{"key":"pgen.1011251.ref062","first-page":"99: 183","article-title":"ALS and FTD: Where RNA metabolism meets protein quality control","author":"J Mandrioli","journal-title":"Semin Cell & Dev Biol"},{"key":"pgen.1011251.ref063","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-020-0250-z","article-title":"Mechanisms, regulation and functions of the unfolded protein response","volume":"21","author":"C Hetz","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pgen.1011251.ref064","doi-asserted-by":"crossref","first-page":"a033894","DOI":"10.1101\/cshperspect.a033894","article-title":"Early Events in the Endoplasmic Reticulum Unfolded Protein Response.","volume":"11","author":"S Preissler","year":"2019","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"pgen.1011251.ref065","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3389\/fnmol.2017.00084","article-title":"Granulostasis: Protein Quality Control of RNP Granules.","volume":"10","author":"S Alberti","year":"2017","journal-title":"Front Mol Neurosci."},{"key":"pgen.1011251.ref066","doi-asserted-by":"crossref","first-page":"e45205","DOI":"10.7554\/eLife.45205","article-title":"Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock","volume":"8","author":"M Azkanaz","year":"2019","journal-title":"Elife"},{"key":"pgen.1011251.ref067","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.60264","article-title":"Protein phase separation and its role in tumorigenesis.","volume":"9","author":"S Jiang","year":"2020","journal-title":"Elife."},{"key":"pgen.1011251.ref068","first-page":"13","article-title":"Phase-to-Phase With Nucleoli\u2013Stress Responses, Protein Aggregation and Novel Roles of RNA.","author":"L. Latonen","year":"2019","journal-title":"Front Cell Neurosci"},{"key":"pgen.1011251.ref069","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41586-021-03985-3","article-title":"The cellular environment shapes the nuclear pore complex architecture","volume":"598","author":"AP Schuller","year":"2021","journal-title":"Nature"},{"key":"pgen.1011251.ref070","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1093\/nar\/gkz168","article-title":"Uncoupling of nucleo-cytoplasmic RNA export and localization during stress","volume":"47","author":"H Hochberg-Laufer","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pgen.1011251.ref071","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.cell.2018.03.025","article-title":"Stress Granule Assembly Disrupts Nucleocytoplasmic Transport","volume":"173","author":"K Zhang","year":"2018","journal-title":"Cell"},{"key":"pgen.1011251.ref072","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nature22038","article-title":"Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice","volume":"544","author":"LA Becker","year":"2017","journal-title":"Nature"},{"key":"pgen.1011251.ref073","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/ng.2853","article-title":"Therapeutic modulation of eIF2\u03b1 phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models","volume":"46","author":"HJ Kim","year":"2014","journal-title":"Nat Genet"},{"key":"pgen.1011251.ref074","doi-asserted-by":"crossref","DOI":"10.1093\/g3journal\/jkab355","article-title":"A C-terminal ataxin-2 disordered region promotes Huntingtin protein aggregation and neurodegeneration in Drosophila models of Huntington\u2019s disease.","volume":"11","author":"J Huelsmeier","year":"2021","journal-title":"G3 (Bethesda)"},{"key":"pgen.1011251.ref075","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1093\/genetics\/165.3.1233","article-title":"Genetic Modifiers of Tauopathy in Drosophila","volume":"165","author":"JM Shulman","year":"2003","journal-title":"Genetics"},{"key":"pgen.1011251.ref076","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.cell.2016.10.002","article-title":"C9orf72 Dipeptide Repeats Impair the Assembly, Dynamics, and Function of Membrane-Less Organelles","volume":"167","author":"K-H Lee","year":"2016","journal-title":"Cell"},{"key":"pgen.1011251.ref077","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nature22044","article-title":"Antisense oligonucleotide therapy for spinocerebellar ataxia type 2","volume":"544","author":"DR Scoles","year":"2017","journal-title":"Nature"},{"key":"pgen.1011251.ref078","unstructured":"Biogen. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04494256. 2021."},{"key":"pgen.1011251.ref079","doi-asserted-by":"crossref","first-page":"111508","DOI":"10.1016\/j.celrep.2022.111508","article-title":"Genome-wide CRISPR screen reveals v-ATPase as a drug target to lower levels of ALS protein ataxin-2","volume":"41","author":"G Kim","year":"2022","journal-title":"Cell Rep"},{"key":"pgen.1011251.ref080","doi-asserted-by":"crossref","first-page":"111505","DOI":"10.1016\/j.celrep.2022.111505","article-title":"Targeting RTN4\/NoGo-Receptor reduces levels of ALS protein ataxin-2","volume":"41","author":"CM Rodriguez","year":"2022","journal-title":"Cell Rep"},{"key":"pgen.1011251.ref081","first-page":"1","article-title":"ll Review ALS Genetics: Gains, Losses, and Implications for Future Therapies","author":"G Kim","year":"2020","journal-title":"Neuron"},{"key":"pgen.1011251.ref082","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1016\/j.molcel.2023.05.025","article-title":"Poly(A)-binding protein is an ataxin-2 chaperone that regulates biomolecular condensates","volume":"83","author":"S Boeynaems","year":"2023","journal-title":"Mol Cell"},{"key":"pgen.1011251.ref083","first-page":"1","article-title":"Antagonistic roles for Ataxin-2 structured and disordered domains in RNP condensation.","volume":"2","author":"A Singh","year":"2021"},{"key":"pgen.1011251.ref084","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1093\/hmg\/ddl173","article-title":"Ataxin-2 and its Drosophila homolog, ATX2, physically assemble with polyribosomes","volume":"15","author":"TF Satterfield","year":"2006","journal-title":"Hum Mol Genet"},{"key":"pgen.1011251.ref085","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1186\/1756-0500-7-453","article-title":"Insights into the evolution and domain structure of Ataxin-2 proteins across eukaryotes.","volume":"7","author":"D Jim\u00e9nez-L\u00f3pez","year":"2014","journal-title":"BMC Res Notes."},{"key":"pgen.1011251.ref086","doi-asserted-by":"crossref","first-page":"e50134","DOI":"10.1371\/journal.pone.0050134","article-title":"Ataxin-2-Like Is a Regulator of Stress Granules and Processing Bodies.","volume":"7","author":"C Kaehler","year":"2012","journal-title":"PLoS One"},{"key":"pgen.1011251.ref087","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.cell.2016.03.007","article-title":"TRIBE: Hijacking an RNA-Editing Enzyme to Identify Cell-Specific Targets of RNA-Binding Proteins","volume":"165","author":"AC McMahon","year":"2016","journal-title":"Cell"},{"key":"pgen.1011251.ref088","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S0092-8674(00)81517-2","article-title":"Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein.","volume":"98","author":"RC Deo","year":"1999","journal-title":"Cell"},{"key":"pgen.1011251.ref089","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/nature24058","article-title":"Radically truncated MeCP2 rescues Rett syndrome-like neurological defects","volume":"550","author":"R Tillotson","year":"2017","journal-title":"Nature"},{"key":"pgen.1011251.ref090","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jmb.2010.01.032","article-title":"Molecular Determinants of PAM2 Recognition by the MLLE Domain of Poly(A)-Binding Protein.","volume":"397","author":"G Kozlov","year":"2010","journal-title":"J Mol Biol"},{"key":"pgen.1011251.ref091","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.bbagrm.2014.08.001","article-title":"The \u201ctale\u201d of poly(A) binding protein: The MLLE domain and PAM2-containing proteins.","volume":"1839","author":"J Xie","year":"2014","journal-title":"Biochim Biophys Acta\u2014Gene Regul Mech"},{"key":"pgen.1011251.ref092","doi-asserted-by":"crossref","first-page":"15810","DOI":"10.1074\/jbc.RA120.013835","article-title":"Direct evidence that Ataxin-2 is a translational activator mediating cytoplasmic polyadenylation","volume":"295","author":"H Inagaki","year":"2020","journal-title":"J Biol Chem"},{"key":"pgen.1011251.ref093","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/gb-2003-4-7-223","article-title":"Poly(A)-binding proteins: multifunctional scaffolds for the post-transcriptional control of gene expression.","volume":"4","author":"DA Mangus","year":"2003","journal-title":"Genome Biol"},{"key":"pgen.1011251.ref094","doi-asserted-by":"crossref","first-page":"e1002920","DOI":"10.1371\/journal.pgen.1002920","article-title":"ATXN2-CAG42 Sequesters PABPC1 into Insolubility and Induces FBXW8 in Cerebellum of Old Ataxic Knock-In Mice.","volume":"8","author":"E Damrath","year":"2012","journal-title":"PLoS Genet"},{"key":"pgen.1011251.ref095","doi-asserted-by":"crossref","first-page":"7115","DOI":"10.1074\/jbc.TM118.001192","article-title":"The molecular language of membraneless organelles","volume":"294","author":"E Gomes","year":"2018","journal-title":"J Biol Chem"},{"key":"pgen.1011251.ref096","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/nature02521","article-title":"Splicing of oskar RNA in the nucleus is coupled to its cytoplasmic localization","volume":"428","author":"O Hachet","year":"2004","journal-title":"Nature"},{"key":"pgen.1011251.ref097","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrm.2017.10","article-title":"The code and beyond: transcription regulation by the RNA polymerase II carboxy-terminal domain","volume":"18","author":"KM Harlen","year":"2017","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pgen.1011251.ref098","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.molcel.2015.08.018","article-title":"Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins","volume":"60","author":"Y Lin","year":"2015","journal-title":"Mol Cell"},{"key":"pgen.1011251.ref099","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/416499a","article-title":"An extensive network of coupling among gene expression machines","volume":"416","author":"T Maniatis","year":"2002","journal-title":"Nature"},{"key":"pgen.1011251.ref100","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1126\/science.1234785","article-title":"ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila","volume":"340","author":"C Lim","year":"2013","journal-title":"Science (80-)."},{"key":"pgen.1011251.ref101","doi-asserted-by":"crossref","first-page":"E655","DOI":"10.1073\/pnas.1107198108","article-title":"The Ataxin-2 protein is required for microRNA function and synapse-specific long-term olfactory habituation","volume":"108","author":"C McCann","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1011251.ref102","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1091\/mbc.e06-12-1120","article-title":"Ataxin-2 interacts with the DEAD\/H-box RNA helicase DDX6 and interferes with P-bodies and stress granules","volume":"18","author":"U Nonhoff","year":"2007","journal-title":"Mol Biol Cell"},{"key":"pgen.1011251.ref103","doi-asserted-by":"crossref","first-page":"E99","DOI":"10.1073\/pnas.1309543111","article-title":"FMRP and Ataxin-2 function together in long-term olfactory habituation and neuronal translational control","volume":"111","author":"IP Sudhakaran","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1011251.ref104","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.molcel.2014.05.022","article-title":"Direct binding of Ataxin-2 to distinct elements in 3\u2019 UTRs promotes mRNA stability and protein expression","volume":"55","author":"M Yokoshi","year":"2014","journal-title":"Mol Cell"},{"key":"pgen.1011251.ref105","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1126\/science.1234746","article-title":"A role for Drosophila ATX2 in activation of PER translation and circadian behavior","volume":"340","author":"Y Zhang","year":"2013","journal-title":"Science"},{"key":"pgen.1011251.ref106","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.molcel.2017.03.004","article-title":"LSM12 and ME31B\/DDX6 Define Distinct Modes of Posttranscriptional Regulation by ATAXIN-2 Protein Complex in Drosophila Circadian Pacemaker Neurons","volume":"66","author":"J Lee","year":"2017","journal-title":"Mol Cell"},{"key":"pgen.1011251.ref107","doi-asserted-by":"crossref","first-page":"e97869","DOI":"10.15252\/embj.201797869","article-title":"Molecular architecture of LSM14 interactions involved in the assembly of mRNA silencing complexes","volume":"37","author":"T Brandmann","year":"2018","journal-title":"EMBO J"},{"key":"pgen.1011251.ref108","doi-asserted-by":"crossref","first-page":"9494","DOI":"10.1073\/pnas.0603701103","article-title":"A mechanism of translational repression by competition of Paip2 with eIF4G for poly(A) binding protein (PABP) binding.","volume":"103","author":"MM Karim","year":"2006","journal-title":"Proc Natl Acad Sci"},{"key":"pgen.1011251.ref109","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1038\/sj.emboj.7601079","article-title":"Poly(A) binding protein (PABP) homeostasis is mediated by the stability of its inhibitor, Paip2.","volume":"25","author":"M Yoshida","year":"2006","journal-title":"EMBO J"},{"key":"pgen.1011251.ref110","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-35753-1","article-title":"Dynamic interaction of poly(A)-binding protein with the ribosome.","volume":"8","author":"K Machida","year":"2018","journal-title":"Sci Rep."},{"key":"pgen.1011251.ref111","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.molcel.2018.05.009","article-title":"PABP Cooperates with the CCR4-NOT Complex to Promote mRNA Deadenylation and Block Precocious Decay","volume":"70","author":"H Yi","year":"2018","journal-title":"Mol Cell"},{"key":"pgen.1011251.ref112","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1515\/hsz-2018-0141","article-title":"Neuronal RNP granules: from physiological to pathological assemblies","volume":"399","author":"F De Graeve","year":"2018","journal-title":"Biol Chem"},{"key":"pgen.1011251.ref113","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/s41586-018-0665-2","article-title":"TDP-43 and RNA form amyloid-like myo-granules in regenerating muscle","volume":"563","author":"TO Vogler","year":"2018","journal-title":"Nature"},{"key":"pgen.1011251.ref114","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1083\/jcb.201508028","article-title":"G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits","volume":"212","author":"N Kedersha","year":"2016","journal-title":"J Cell Biol"},{"key":"pgen.1011251.ref115","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.celrep.2018.01.036","article-title":"Intrinsically Disordered Regions Can Contribute Promiscuous Interactions to RNP Granule Assembly","volume":"22","author":"DSW Protter","year":"2018","journal-title":"Cell Rep"},{"key":"pgen.1011251.ref116","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nature22386","article-title":"RNA phase transitions in repeat expansion disorders","volume":"546","author":"A Jain","year":"2017","journal-title":"Nature"},{"key":"pgen.1011251.ref117","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","article-title":"TopHat: discovering splice junctions with RNA-Seq","volume":"25","author":"C Trapnell","year":"2009","journal-title":"Bioinformatics"},{"key":"pgen.1011251.ref118","doi-asserted-by":"crossref","first-page":"190087","DOI":"10.1098\/rsob.190087","article-title":"Adult Drosophila muscle morphometry through microCT reveals dynamics during ageing.","volume":"9","author":"D Chaturvedi","year":"2019","journal-title":"Open Biol."}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1011251","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011251","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T14:36:30Z","timestamp":1718116590000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011251"}},"subtitle":[],"editor":[{"given":"Giovanni","family":"Bosco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,20]]},"references-count":118,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1011251","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.02.15.480566","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,20]]}}}