{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:38:31Z","timestamp":1790807911496,"version":"4.1.0"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R21NS109412-02"],"award-info":[{"award-number":["5R21NS109412-02"]}],"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":["5R01NS08645208"],"award-info":[{"award-number":["5R01NS08645208"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Huntington\u2019s disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the HD gene, coding for huntingtin protein (HTT). Mechanisms of HD cellular pathogenesis remain undefined and likely involve disruptions in many cellular processes and functions presumably mediated by abnormal protein interactions of mutant HTT. We previously found HTT interaction with several protein arginine methyl-transferase (PRMT) enzymes. Protein arginine methylation mediated by PRMT enzymes is an important post-translational modification with an emerging role in neurodegeneration. We found that normal (but not mutant) HTT can facilitate the activity of PRMTs in vitro and the formation of arginine methylation complexes. These interactions appear to be disrupted in HD neurons. This suggests an additional functional role for HTT\/PRMT interactions, not limited to substrate\/enzyme relationship, which may result in global changes in arginine protein methylation in HD. Our quantitative analysis of striatal precursor neuron proteome indicated that arginine protein methylation is significantly altered in HD. We identified a cluster highly enriched in RNA-binding proteins with reduced arginine methylation, which is essential to their function in RNA processing and splicing. We found that several of these proteins interact with HTT, and their RNA-binding and localization are affected in HD cells likely due to a compromised arginine methylation and\/or abnormal interactions with mutant HTT. These studies reveal a potential new mechanism for disruption of RNA processing in HD, involving a direct interaction of HTT with methyl-transferase enzymes and modulation of their activity and highlighting methylation of arginine as potential new therapeutic target for HD.<\/jats:p>","DOI":"10.1093\/hmg\/ddad125","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T15:59:19Z","timestamp":1690991959000},"page":"3006-3025","source":"Crossref","is-referenced-by-count":8,"title":["Arginine methylation of RNA-binding proteins is impaired in Huntington\u2019s disease"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4020-5644","authenticated-orcid":false,"given":"Tamara","family":"Ratovitski","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences , Division of Neurobiology, , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University , Division of Neurobiology, , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhi V","family":"Kamath","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences , Division of Neurobiology, , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University , Division of Neurobiology, , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N","family":"O'Meally","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry , Mass Spectrometry and Proteomics Facility, , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University , Mass Spectrometry and Proteomics Facility, , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keerthana","family":"Gosala","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences , Division of Neurobiology, , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University , Division of Neurobiology, , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe D","family":"Holland","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences , Division of Neurobiology, , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University , Division of Neurobiology, , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mali","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences , Division of Neurobiology, , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University , Division of Neurobiology, , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry , Mass Spectrometry and Proteomics Facility, , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University , Mass Spectrometry and Proteomics Facility, , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences , Division of Neurobiology, , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University , Division of Neurobiology, , Baltimore, MD 21287 , USA"},{"name":"Departments of Neurology , Neuroscience and Pharmacology, , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University , Neuroscience and Pharmacology, , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"2023100414290821800_ref1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes","volume":"72","author":"The Huntington's Disease Collaborative Research Group","year":"1993","journal-title":"Cell"},{"key":"2023100414290821800_ref2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrneurol.2014.24","article-title":"Huntington disease: natural history, biomarkers and prospects for therapeutics","volume":"10","author":"Ross","year":"2014","journal-title":"Nat. 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