{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:19:46Z","timestamp":1792091986879,"version":"4.4.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"7657","license":[{"start":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T00:00:00Z","timestamp":1496188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T00:00:00Z","timestamp":1496188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2017,6,8]]},"DOI":"10.1038\/nature22386","type":"journal-article","created":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T05:01:53Z","timestamp":1496206913000},"page":"243-247","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":934,"title":["RNA phase transitions in repeat expansion disorders"],"prefix":"10.1038","volume":"546","author":[{"given":"Ankur","family":"Jain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald D.","family":"Vale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,31]]},"reference":[{"key":"BFnature22386_CR1","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/nrg1691","volume":"6","author":"JR Gatchel","year":"2005","unstructured":"Gatchel, J. R. & Zoghbi, H. Y. Diseases of unstable repeat expansion: mechanisms and common principles. Nat. Rev. Genet. 6, 743\u2013755 (2005)","journal-title":"Nat. Rev. Genet."},{"key":"BFnature22386_CR2","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nrg2748","volume":"11","author":"AR La Spada","year":"2010","unstructured":"La Spada, A. R. & Taylor, J. P. Repeat expansion disease: progress and puzzles in disease pathogenesis. Nat. Rev. Genet. 11, 247\u2013258 (2010)","journal-title":"Nat. Rev. Genet."},{"key":"BFnature22386_CR3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1093\/nar\/gkr729","volume":"40","author":"WJ Krzyzosiak","year":"2012","unstructured":"Krzyzosiak, W. J. et al. Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target. Nucleic Acids Res. 40, 11\u201326 (2012)","journal-title":"Nucleic Acids Res."},{"key":"BFnature22386_CR4","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","volume":"72","author":"M DeJesus-Hernandez","year":"2011","unstructured":"DeJesus-Hernandez, M. et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245\u2013256 (2011)","journal-title":"Neuron"},{"key":"BFnature22386_CR5","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","volume":"72","author":"AE Renton","year":"2011","unstructured":"Renton, A. E. et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257\u2013268 (2011)","journal-title":"Neuron"},{"key":"BFnature22386_CR6","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.gde.2014.07.003","volume":"26","author":"D-Y Lee","year":"2014","unstructured":"Lee, D.-Y. & McMurray, C. T. Trinucleotide expansion in disease: why is there a length threshold? Curr. Opin. Genet. Dev. 26, 131\u2013140 (2014)","journal-title":"Curr. Opin. Genet. Dev."},{"key":"BFnature22386_CR7","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1126\/science.aaa9344","volume":"348","author":"J Chew","year":"2015","unstructured":"Chew, J. et al. Neurodegeneration. C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits. Science 348, 1151\u20131154 (2015)","journal-title":"Science"},{"key":"BFnature22386_CR8","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1126\/science.289.5485.1769","volume":"289","author":"A Mankodi","year":"2000","unstructured":"Mankodi, A. et al. Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science 289, 1769\u20131773 (2000)","journal-title":"Science"},{"key":"BFnature22386_CR9","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/S0896-6273(03)00533-6","volume":"39","author":"P Jin","year":"2003","unstructured":"Jin, P. et al. RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. Neuron 39, 739\u2013747 (2003)","journal-title":"Neuron"},{"key":"BFnature22386_CR10","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1073\/pnas.1013343108","volume":"108","author":"T Zu","year":"2011","unstructured":"Zu, T. et al. Non-ATG-initiated translation directed by microsatellite expansions. Proc. Natl Acad. Sci. USA 108, 260\u2013265 (2011)","journal-title":"Proc. Natl Acad. Sci. USA"},{"issue":"R1","key":"BFnature22386_CR11","doi-asserted-by":"publisher","first-page":"R45","DOI":"10.1093\/hmg\/ddt371","volume":"22","author":"JD Cleary","year":"2013","unstructured":"Cleary, J. D. & Ranum, L. P. W. Repeat-associated non-ATG (RAN) translation in neurological disease. Hum. Mol. Genet. 22 (R1), R45\u2013R51 (2013)","journal-title":"Hum. Mol. Genet."},{"key":"BFnature22386_CR12","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1083\/jcb.128.6.995","volume":"128","author":"KL Taneja","year":"1995","unstructured":"Taneja, K. L., McCurrach, M., Schalling, M., Housman, D. & Singer, R. H. Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues. J. Cell Biol. 128, 995\u20131002 (1995)","journal-title":"J. Cell Biol."},{"key":"BFnature22386_CR13","doi-asserted-by":"publisher","first-page":"3811","DOI":"10.1093\/hmg\/ddr299","volume":"20","author":"M Wojciechowska","year":"2011","unstructured":"Wojciechowska, M. & Krzyzosiak, W. J. Cellular toxicity of expanded RNA repeats: focus on RNA foci. Hum. Mol. Genet. 20, 3811\u20133821 (2011)","journal-title":"Hum. Mol. Genet."},{"key":"BFnature22386_CR14","doi-asserted-by":"publisher","first-page":"4439","DOI":"10.1093\/emboj\/19.17.4439","volume":"19","author":"JW Miller","year":"2000","unstructured":"Miller, J. W. et al. Recruitment of human muscleblind proteins to (CUG)n expansions associated with myotonic dystrophy. EMBO J. 19, 4439\u20134448 (2000)","journal-title":"EMBO J."},{"key":"BFnature22386_CR15","doi-asserted-by":"publisher","first-page":"345","DOI":"10.7554\/eLife.17820","volume":"5","author":"EG Conlon","year":"2016","unstructured":"Conlon, E. G. et al. The C9ORF72 GGGGCC expansion forms RNA G-quadruplex inclusions and sequesters hnRNP H to disrupt splicing in ALS brains. eLife 5, 345 (2016)","journal-title":"eLife"},{"key":"BFnature22386_CR16","doi-asserted-by":"publisher","first-page":"7820","DOI":"10.1074\/jbc.M005960200","volume":"276","author":"NA Timchenko","year":"2001","unstructured":"Timchenko, N. A. et al. RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1. J. Biol. Chem. 276, 7820\u20137826 (2001)","journal-title":"J. Biol. Chem."},{"key":"BFnature22386_CR17","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/ana.21948","volume":"67","author":"PK Todd","year":"2010","unstructured":"Todd, P. K. & Paulson, H. L. RNA-mediated neurodegeneration in repeat expansion disorders. Ann. Neurol. 67, 291\u2013300 (2010)","journal-title":"Ann. Neurol."},{"key":"BFnature22386_CR18","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.mcn.2012.12.006","volume":"56","author":"VV Belzil","year":"2013","unstructured":"Belzil, V. V., Gendron, T. F. & Petrucelli, L. RNA-mediated toxicity in neurodegenerative disease. Mol. Cell. Neurosci. 56, 406\u2013419 (2013)","journal-title":"Mol. Cell. Neurosci."},{"key":"BFnature22386_CR19","unstructured":"Flory, P. J. Principles of Polymer Chemistry (Cornell Univ. Press, 1953)"},{"key":"BFnature22386_CR20","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/nature10879","volume":"483","author":"P Li","year":"2012","unstructured":"Li, P. et al. Phase transitions in the assembly of multivalent signalling proteins. Nature 483, 336\u2013340 (2012)","journal-title":"Nature"},{"key":"BFnature22386_CR21","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1063\/1.1723922","volume":"12","author":"WH Stockmayer","year":"1944","unstructured":"Stockmayer, W. H. Theory of molecular size distribution and gel formation in branched polymers II. General cross linking. J. Chem. Phys. 12, 125\u2013131 (1944)","journal-title":"J. Chem. Phys."},{"key":"BFnature22386_CR22","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1021\/ma970616h","volume":"31","author":"AN Semenov","year":"1998","unstructured":"Semenov, A. N. & Rubinstein, M. Thermoreversible gelation in solutions of associative polymers. 1. Statics. Macromolecules 31, 1373\u20131385 (1998)","journal-title":"Statics. Macromolecules"},{"key":"BFnature22386_CR23","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1016\/j.bpj.2013.10.016","volume":"105","author":"CV Falkenberg","year":"2013","unstructured":"Falkenberg, C. V., Blinov, M. L. & Loew, L. M. Pleomorphic ensembles: formation of large clusters composed of weakly interacting multivalent molecules. Biophys. J. 105, 2451\u20132460 (2013)","journal-title":"Biophys. J."},{"key":"BFnature22386_CR24","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/nchem.2414","volume":"8","author":"WM Aumiller Jr","year":"2016","unstructured":"Aumiller, W. M. Jr & Keating, C. D. Phosphorylation-mediated RNA\/peptide complex coacervation as a model for intracellular liquid organelles. Nat. Chem. 8, 129\u2013137 (2016)","journal-title":"Nat. Chem."},{"key":"BFnature22386_CR25","unstructured":"Larson, R. G. The Structure and Rheology of Complex Fluids (Oxford Univ. Press, 1999)"},{"key":"BFnature22386_CR26","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/S1097-2765(00)80143-4","volume":"2","author":"E Bertrand","year":"1998","unstructured":"Bertrand, E. et al. Localization of ASH1 mRNA particles in living yeast. Mol. Cell 2, 437\u2013445 (1998)","journal-title":"Mol. Cell"},{"key":"BFnature22386_CR27","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.molcel.2016.02.034","volume":"62","author":"MG Kearse","year":"2016","unstructured":"Kearse, M. G. et al. CGG repeat-associated non-AUG translation utilizes a cap-dependent scanning mechanism of initiation to produce toxic proteins. Mol. Cell 62, 314\u2013322 (2016)","journal-title":"Mol. Cell"},{"key":"BFnature22386_CR28","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1126\/science.1172046","volume":"324","author":"CP Brangwynne","year":"2009","unstructured":"Brangwynne, C. P. et al. Germline P granules are liquid droplets that localize by controlled dissolution\/condensation. Science 324, 1729\u20131732 (2009)","journal-title":"Science"},{"key":"BFnature22386_CR29","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/j.bbadis.2016.05.015","volume":"1862","author":"MO Urbanek","year":"2016","unstructured":"Urbanek, M. O., Jazurek, M., Switonski, P. M., Figura, G. & Krzyzosiak, W. J. Nuclear speckles are detention centers for transcripts containing expanded CAG repeats. Biochim. Biophys. Acta 1862, 1513\u20131520 (2016)","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnature22386_CR30","doi-asserted-by":"publisher","first-page":"a000646","DOI":"10.1101\/cshperspect.a000646","volume":"3","author":"DL Spector","year":"2011","unstructured":"Spector, D. L. & Lamond, A. I. Nuclear speckles. Cold Spring Harb. Perspect. Biol. 3, a000646 (2011)","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"BFnature22386_CR31","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1038\/nature06909","volume":"453","author":"L-B Li","year":"2008","unstructured":"Li, L.-B., Yu, Z., Teng, X. & Bonini, N. M. RNA toxicity is a component of ataxin-3 degeneration in Drosophila. Nature 453, 1107\u20131111 (2008)","journal-title":"Nature"},{"key":"BFnature22386_CR32","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1038\/nmeth.1253","volume":"5","author":"A Raj","year":"2008","unstructured":"Raj, A., van den Bogaard, P., Rifkin, S. A., van Oudenaarden, A. & Tyagi, S. Imaging individual mRNA molecules using multiple singly labeled probes. Nat. Methods 5, 877\u2013879 (2008)","journal-title":"Nat. Methods"},{"key":"BFnature22386_CR33","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1247\/csf.22.387","volume":"22","author":"MS Hamaguchi","year":"1997","unstructured":"Hamaguchi, M. S., Watanabe, K. & Hamaguchi, Y. Regulation of intracellular pH in sea urchin eggs by medium containing both weak acid and base. Cell Struct. Funct. 22, 387\u2013398 (1997)","journal-title":"Cell Struct. Funct."},{"key":"BFnature22386_CR34","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1146\/annurev.pharmtox.010909.105654","volume":"50","author":"CF Bennett","year":"2010","unstructured":"Bennett, C. F. & Swayze, E. E. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol. 50, 259\u2013293 (2010)","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"BFnature22386_CR35","doi-asserted-by":"publisher","first-page":"2538","DOI":"10.1021\/bi00462a016","volume":"29","author":"CA Frederick","year":"1990","unstructured":"Frederick, C. A. et al. Structural comparison of anticancer drug\u2013DNA complexes: adriamycin and daunomycin. Biochemistry 29, 2538\u20132549 (1990)","journal-title":"Biochemistry"},{"key":"BFnature22386_CR36","doi-asserted-by":"publisher","first-page":"9860","DOI":"10.1074\/jbc.C113.452532","volume":"288","author":"K Reddy","year":"2013","unstructured":"Reddy, K., Zamiri, B., Stanley, S. Y. R., Macgregor, R. B. Jr & Pearson, C. E. The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures. J. Biol. Chem. 288, 9860\u20139866 (2013)","journal-title":"J. Biol. Chem."},{"key":"BFnature22386_CR37","doi-asserted-by":"publisher","first-page":"aaf5371","DOI":"10.1126\/science.aaf5371","volume":"353","author":"JU Guo","year":"2016","unstructured":"Guo, J. U. & Bartel, D. P. RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria. Science 353, aaf5371 (2016)","journal-title":"Science"},{"key":"BFnature22386_CR38","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1146\/annurev-cellbio-100913-013325","volume":"30","author":"AA Hyman","year":"2014","unstructured":"Hyman, A. A., Weber, C. A. & J\u00fclicher, F. Liquid\u2013liquid phase separation in biology. Annu. Rev. Cell Dev. Biol. 30, 39\u201358 (2014)","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"BFnature22386_CR39","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/ng760","volume":"29","author":"SE Holmes","year":"2001","unstructured":"Holmes, S. E. et al. A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2. Nat. Genet. 29, 377\u2013378 (2001)","journal-title":"Nat. Genet."},{"key":"BFnature22386_CR40","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nature09320","volume":"466","author":"AC Elden","year":"2010","unstructured":"Elden, A. C. et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466, 1069\u20131075 (2010)","journal-title":"Nature"},{"key":"BFnature22386_CR41","doi-asserted-by":"publisher","first-page":"13428","DOI":"10.1073\/pnas.1204089109","volume":"109","author":"H Tsoi","year":"2012","unstructured":"Tsoi, H., Lau, T. C.-K., Tsang, S.-Y., Lau, K.-F. & Chan, H. Y. E. CAG expansion induces nucleolar stress in polyglutamine diseases. Proc. Natl Acad. Sci. USA 109, 13428\u201313433 (2012)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature22386_CR42","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/nature14974","volume":"525","author":"BD Freibaum","year":"2015","unstructured":"Freibaum, B. D. et al. GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature 525, 129\u2013133 (2015)","journal-title":"Nature"},{"key":"BFnature22386_CR43","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature14973","volume":"525","author":"K Zhang","year":"2015","unstructured":"Zhang, K. et al. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525, 56\u201361 (2015)","journal-title":"Nature"},{"key":"BFnature22386_CR44","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/1472-6750-11-87","volume":"11","author":"A Scior","year":"2011","unstructured":"Scior, A., Preissler, S., Koch, M. & Deuerling, E. Directed PCR-free engineering of highly repetitive DNA sequences. BMC Biotechnol. 11, 87 (2011)","journal-title":"BMC Biotechnol."},{"key":"BFnature22386_CR45","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/nature10016","volume":"473","author":"A Jain","year":"2011","unstructured":"Jain, A. et al. Probing cellular protein complexes using single-molecule pull-down. Nature 473, 484\u2013488 (2011)","journal-title":"Nature"},{"key":"BFnature22386_CR46","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1126\/science.1099754","volume":"304","author":"Y Shav-Tal","year":"2004","unstructured":"Shav-Tal, Y. et al. Dynamics of single mRNPs in nuclei of living cells. Science 304, 1797\u20131800 (2004)","journal-title":"Science"},{"key":"BFnature22386_CR47","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/S0076-6879(03)75025-3","volume":"375","author":"RD Phair","year":"2004","unstructured":"Phair, R. D., Gorski, S. A. & Misteli, T. Measurement of dynamic protein binding to chromatin in vivo, using photobleaching microscopy. Methods Enzymol. 375, 393\u2013414 (2004)","journal-title":"Methods Enzymol."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/nature22386.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/nature22386","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nature22386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/nature22386.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T08:54:34Z","timestamp":1719219274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature22386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,31]]},"references-count":47,"journal-issue":{"issue":"7657","published-print":{"date-parts":[[2017,6,8]]}},"alternative-id":["BFnature22386"],"URL":"https:\/\/doi.org\/10.1038\/nature22386","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727678154.793536159","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.727678154.793534433","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/100719","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,31]]},"assertion":[{"value":"11 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}