{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:49:36Z","timestamp":1792205376608,"version":"4.4.0"},"reference-count":64,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T00:00:00Z","timestamp":1473724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T00:00:00Z","timestamp":1473724800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T00:00:00Z","timestamp":1473724800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["Training Grant"],"award-info":[{"award-number":["Training Grant"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T32GM008798"],"award-info":[{"award-number":["5T32GM008798"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001441","name":"Judith and Jean Pape Adams Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001441","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS07377"],"award-info":[{"award-number":["R01 NS07377"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Columbia Motor Neuron Center","award":["Starter grant"],"award-info":[{"award-number":["Starter grant"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 GM 118136"],"award-info":[{"award-number":["R35 GM 118136"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM48259"],"award-info":[{"award-number":["R01 GM48259"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Columbia Motor Neuron Center"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    An expanded GGGGCC hexanucleotide in\n                    <jats:italic>C9ORF72<\/jats:italic>\n                    (C9) is the most frequent known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It has been proposed that expanded transcripts adopt G-quadruplex (G-Q) structures and associate with proteins, but whether this occurs and contributes to disease is unknown. Here we show first that the protein that predominantly associates with GGGGCC repeat RNA in vitro is the splicing factor hnRNP H, and that this interaction is linked to G-Q formation. We then show that G-Q RNA foci are more abundant in C9 ALS patient fibroblasts and astrocytes compared to those without the expansion, and more frequently colocalize with hnRNP H. Importantly, we demonstrate dysregulated splicing of multiple known hnRNP H-target transcripts in C9 patient brains, which correlates with elevated insoluble hnRNP H\/G-Q aggregates. Together, our data implicate C9 expansion-mediated sequestration of hnRNP H as a significant contributor to neurodegeneration in C9 ALS\/FTD.\n                  <\/jats:p>","DOI":"10.7554\/elife.17820","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T08:00:48Z","timestamp":1473753648000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.17820","source":"Crossref","is-referenced-by-count":280,"title":["The C9ORF72 GGGGCC expansion forms RNA G-quadruplex inclusions and sequesters hnRNP H to disrupt splicing in ALS brains"],"prefix":"10.7554","volume":"5","author":[{"given":"Erin G","family":"Conlon","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University Medical Center, New York, United 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