{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:28:22Z","timestamp":1787300902838,"version":"build-2736575974"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"The Inter-University Research Network for High Depth Omics, Institute of Molecular Embryology and Genetics, Kumamoto University"},{"name":"International Research Core for Stem Cell-based Developmental Medicine Encourage Project"},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Astellas Foundation for Research on Metabolic Disorders"},{"DOI":"10.13039\/501100005865","name":"the Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Narishige Neuroscience Research Foundation"},{"DOI":"10.13039\/501100004088","name":"Kowa Life Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004088","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Pharmacological Research Foundation, Tokyo"},{"name":"MEXT Promotion of Development of a Joint Usage\/Research System Project: Coalition of Universities for Research Excellence Program","award":["JPMXP1323015486"],"award-info":[{"award-number":["JPMXP1323015486"]}]},{"name":"JST FOREST Program","award":["JPMJFR2043"],"award-info":[{"award-number":["JPMJFR2043"]}]},{"name":"JSPS KAKENHI","award":["JP21H00207, JP20K21400, JP22K19297 and JP23H00373"],"award-info":[{"award-number":["JP21H00207, JP20K21400, JP22K19297 and JP23H00373"]}]},{"name":"JSPS KAKENHI","award":["JP21K06579 and JP23H03851"],"award-info":[{"award-number":["JP21K06579 and JP23H03851"]}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP22ek0109591 and JP23ek0109651"],"award-info":[{"award-number":["JP22ek0109591 and JP23ek0109651"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP21gm6410021"],"award-info":[{"award-number":["JP21gm6410021"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP21wm0525023"],"award-info":[{"award-number":["JP21wm0525023"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neurodegenerative disorders, including Alzheimer\u2019s disease and Parkinson\u2019s disease, are becoming increasingly prevalent in super-ageing societies. However, the molecular mechanisms by which prion-like proteins undergo aberrant phase transition, aggregation and propagation during neurodegeneration remain incompletely understood. Although these proteins are capable of undergoing liquid\u2013liquid phase separation (LLPS), followed by a sol\u2013gel transition in vitro, the factors that govern their pathological phase transition in vivo remain largely elusive. Notably, many prion-like proteins also possess RNA-binding properties, and accumulating evidence indicates that RNA plays pivotal roles in regulating both LLPS and the subsequent transition to more solid-like states. In this review, we summarize recent advances in the RNA structural biology of neurodegeneration, with particular emphasis on RNA G-quadruplexes (rG4s) as pathological determinants and discuss emerging mechanisms by which RNA structures promote the phase transition and proteinopathy of prion-like proteins.<\/jats:p>","DOI":"10.1093\/jb\/mvag040","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:20:32Z","timestamp":1780917632000},"page":"179-184","source":"Crossref","is-referenced-by-count":0,"title":["RNA structural biology of neurodegeneration: phase separation, phase transition and proteinopathy"],"prefix":"10.1093","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-6591","authenticated-orcid":false,"given":"Yasushi","family":"Yabuki","sequence":"first","affiliation":[{"name":"Department of Genomic Neurology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University , 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 ,","place":["Japan"]},{"name":"Graduate School of Pharmaceutical Sciences, Kumamoto University , 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9012-8328","authenticated-orcid":false,"given":"Norifumi","family":"Shioda","sequence":"additional","affiliation":[{"name":"Department of Genomic Neurology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University , 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 ,","place":["Japan"]},{"name":"Graduate School of Pharmaceutical Sciences, Kumamoto University , 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"2026082104211563800_ref1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nature12481","article-title":"Self-propagation of pathogenic protein aggregates in neurodegenerative diseases","volume":"501","author":"Jucker","year":"2013","journal-title":"Nature"},{"key":"2026082104211563800_ref2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.tins.2019.08.005","article-title":"Physiological, pathological, and targetable membraneless organelles in neurons","volume":"42","author":"Ryan","year":"2019","journal-title":"Trends Neurosci."},{"key":"2026082104211563800_ref3","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/171737a0","article-title":"Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid","volume":"171","author":"Watson","year":"1953","journal-title":"Nature"},{"key":"2026082104211563800_ref4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00018-009-0131-2","article-title":"Non-B DNA structure-induced genetic instability and evolution","volume":"67","author":"Zhao","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"2026082104211563800_ref5","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.3390\/ijms20122884","article-title":"Perspectives for applying G-quadruplex structures in neurobiology and neuropharmacology","volume":"20","author":"Asamitsu","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2026082104211563800_ref6","doi-asserted-by":"crossref","first-page":"4433","DOI":"10.1093\/nar\/gkn402","article-title":"Effect of loop length variation on quadruplex-Watson Crick duplex competition","volume":"36","author":"Kumar","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2026082104211563800_ref7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fchem.2016.00038","article-title":"Metal cations in G-quadruplex folding and stability","volume":"4","author":"Bhattacharyya","year":"2016","journal-title":"Front Chem."},{"key":"2026082104211563800_ref8","doi-asserted-by":"crossref","first-page":"7429","DOI":"10.1093\/nar\/gkm711","article-title":"Human telomere, oncogenic promoter and 5\u2032-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics","volume":"35","author":"Patel","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2026082104211563800_ref9","doi-asserted-by":"crossref","first-page":"7251","DOI":"10.1021\/bi200805j","article-title":"A sequence-independent analysis of the loop length dependence of intramolecular RNA G-quadruplex stability and topology","volume":"50","author":"Zhang","year":"2011","journal-title":"Biochem"},{"key":"2026082104211563800_ref10","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/nmeth.3965","article-title":"rG4-seq reveals widespread formation of G-quadruplex structures in the human transcriptome","volume":"13","author":"Kwok","year":"2016","journal-title":"Nat. Methods."},{"key":"2026082104211563800_ref11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.chembiol.2023.08.010","article-title":"RNA G-quadruplex in functional regulation of noncoding RNA: challenges and emerging opportunities","volume":"31","author":"Sahayasheela","year":"2024","journal-title":"Cell Chem. Biol"},{"key":"2026082104211563800_ref12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cell.2006.09.014","article-title":"Dendritic protein synthesis, synaptic plasticity, and memory","volume":"127","author":"Sutton","year":"2006","journal-title":"Cell"},{"key":"2026082104211563800_ref13","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/embor.2011.76","article-title":"G-quadruplex RNA structure as a signal for neurite mRNA targeting","volume":"12","author":"Subramanian","year":"2011","journal-title":"EMBO Rep."},{"key":"2026082104211563800_ref14","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0896-6273(02)00978-9","article-title":"Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation","volume":"36","author":"Miller","year":"2002","journal-title":"Neuron"},{"key":"2026082104211563800_ref15","doi-asserted-by":"crossref","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":"2026082104211563800_ref16","doi-asserted-by":"crossref","first-page":"eade2035","DOI":"10.1126\/sciadv.ade2035","article-title":"RNA G-quadruplex organizes stress granule assembly through DNAPTP6 in neurons","volume":"9","author":"Asamitsu","year":"2023","journal-title":"Sci. Adv."},{"key":"2026082104211563800_ref17","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1093\/jb\/mvab018","article-title":"Potential roles of G-quadruplex structures in RNA granules for physiological and pathological phase separation","volume":"169","author":"Asamitsu","year":"2021","journal-title":"J. Biochem."},{"key":"2026082104211563800_ref18","article-title":"The role of RNA G-quadruplexes in human diseases and therapeutic strategies","volume":"11","author":"Kharel","year":"2020","journal-title":"Wiley Interdiscip Rev"},{"key":"2026082104211563800_ref19","doi-asserted-by":"crossref","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":"2026082104211563800_ref20","doi-asserted-by":"crossref","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":"2026082104211563800_ref21","doi-asserted-by":"crossref","first-page":"6835","DOI":"10.1016\/j.cell.2024.09.037","article-title":"RNA G-quadruplexes form scaffolds that promote neuropathological \u03b1-synuclein aggregation","volume":"187","author":"Matsuo","year":"2024","journal-title":"Cell"},{"key":"2026082104211563800_ref22","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.107971","article-title":"RNA G-quadruplexes and calcium ions synergistically induce Tau phase transition in vitro","volume":"300","author":"Yabuki","year":"2024","journal-title":"J. Biol. Chem."},{"key":"2026082104211563800_ref23","doi-asserted-by":"crossref","first-page":"679","DOI":"10.2174\/092986606777790566","article-title":"The proline-rich domain and the microtubule binding domain of protein tau acting as RNA binding domains","volume":"13","author":"Wang","year":"2006","journal-title":"Protein Pept. Lett."},{"key":"2026082104211563800_ref24","doi-asserted-by":"crossref","first-page":"RP105446","DOI":"10.7554\/eLife.105446.3","article-title":"Chronic RNA G-quadruplex accumulation in aging and Alzheimer's disease","volume":"14","author":"Kallweit","year":"2025","journal-title":"ELife"},{"key":"2026082104211563800_ref25","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2021.101284","article-title":"ALS-linked FUS mutations dysregulate G-quadruplex-dependent liquid\u2013liquid phase separation and liquid-to-solid transition","volume":"297","author":"Ishiguro","year":"2021","journal-title":"J. Biol. Chem."},{"key":"2026082104211563800_ref26","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/1873-3468.14013","article-title":"Different recognition modes of G-quadruplex RNA between two ALS\/FTLD-linked proteins TDP-43 and FUS","volume":"595","author":"Ishiguro","year":"2021","journal-title":"FEBS Lett."},{"key":"2026082104211563800_ref27","doi-asserted-by":"crossref","DOI":"10.15252\/embr.202153632","article-title":"Specific RNA interactions promote TDP-43 multivalent phase separation and maintain liquid properties","volume":"22","author":"Grese","year":"2021","journal-title":"EMBO Rep."},{"key":"2026082104211563800_ref28","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.str.2025.05.006","article-title":"The effect of G-quadruplexes on TDP43 condensation, distribution, and toxicity","volume":"33","author":"Oldani","year":"2025","journal-title":"Structure"},{"key":"2026082104211563800_ref29","doi-asserted-by":"crossref","first-page":"8272","DOI":"10.1038\/s41467-023-43872-1","article-title":"The ALS\/FTD-related C9orf72 hexanucleotide repeat expansion forms RNA condensates through multimolecular G-quadruplexes","volume":"14","author":"Raguseo","year":"2023","journal-title":"Nat. Commun."},{"key":"2026082104211563800_ref30","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/ncomms2514","article-title":"Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1\u2013PP2A protein complex","volume":"4","author":"Krauss","year":"2013","journal-title":"Nat. Commun."},{"key":"2026082104211563800_ref31","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41586-023-06701-5","article-title":"m1A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration","volume":"623","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"2026082104211563800_ref32","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1261\/rna.610607","article-title":"MBNL binds similar RNA structures in the CUG repeats of myotonic dystrophy and its pre-mRNA substrate cardiac troponin T","volume":"13","author":"Warf","year":"2007","journal-title":"RNA"},{"key":"2026082104211563800_ref33","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1093\/hmg\/10.19.2165","article-title":"Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2","volume":"10","author":"Mankodi","year":"2001","journal-title":"Hum. Mol. Genet."}],"container-title":["The Journal of Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jb\/advance-article-pdf\/doi\/10.1093\/jb\/mvag040\/68508710\/mvag040.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jb\/article-pdf\/180\/3\/179\/68508710\/mvag040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jb\/article-pdf\/180\/3\/179\/68508710\/mvag040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:21:27Z","timestamp":1787300487000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jb\/article\/180\/3\/179\/8705588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6,11]]},"published-print":{"date-parts":[[2026,9,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jb\/mvag040","relation":{},"ISSN":["0021-924X","1756-2651"],"issn-type":[{"value":"0021-924X","type":"print"},{"value":"1756-2651","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,6,11]]}}}