{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:13:11Z","timestamp":1789153991490,"version":"build-2803163510"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000738","name":"VA","doi-asserted-by":"publisher","award":["BLRD BX004842"],"award-info":[{"award-number":["BLRD BX004842"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32NS00722237"],"award-info":[{"award-number":["T32NS00722237"]}],"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":["F31NS113513"],"award-info":[{"award-number":["F31NS113513"]}],"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":["R01NS086810"],"award-info":[{"award-number":["R01NS086810"]}],"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":["R01NS099280"],"award-info":[{"award-number":["R01NS099280"]}],"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":["P50HD104463"],"award-info":[{"award-number":["P50HD104463"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Repeat associated non-AUG (RAN) translation of CGG repeats in the 5\u2032UTR of FMR1 produces toxic proteins that contribute to fragile X-associated tremor\/ataxia syndrome (FXTAS) pathogenesis. The most abundant RAN product, FMRpolyG, initiates predominantly at an ACG upstream of the repeat. Accurate FMRpolyG measurements in FXTAS patients are lacking. We used data-dependent acquisition and parallel reaction monitoring (PRM) mass spectrometry coupled with stable isotope labeled standard peptides to identify signature FMRpolyG fragments in patient samples. Following immunoprecipitation, PRM detected FMRpolyG signature peptides in transfected cells, and FXTAS tissues and cells, but not in controls. We identified two amino-terminal peptides: an ACG-initiated Ac-MEAPLPGGVR and a GUG-initiated Ac-TEAPLPGGVR, as well as evidence for RAN translation initiation within the CGG repeat itself in two reading frames. Initiation at all sites increased following cellular stress, decreased following eIF1 overexpression and was eIF4A and M7G cap-dependent. These data demonstrate that FMRpolyG is quantifiable in human samples and FMR1 RAN translation initiates via similar mechanisms for near-cognate codons and within the repeat through processes dependent on available initiation factors and cellular environment.<\/jats:p>","DOI":"10.1093\/hmg\/ddab353","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T07:06:30Z","timestamp":1642662390000},"page":"2317-2332","source":"Crossref","is-referenced-by-count":19,"title":["Mechanistic convergence across initiation sites for RAN translation in fragile X associated tremor ataxia syndrome"],"prefix":"10.1093","volume":"31","author":[{"given":"Yuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology , University of Michigan, Ann Arbor, MI, USA"},{"name":"Department of Respiratory Medicine , Xiangya Hospital, Central South University, Changsha 410008 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-2894","authenticated-orcid":false,"given":"M Rebecca","family":"Glineburg","sequence":"additional","affiliation":[{"name":"Department of Neurology , University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatesha","family":"Basrur","sequence":"additional","affiliation":[{"name":"Department of Pathology , University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Conlon","sequence":"additional","affiliation":[{"name":"Department of Pathology , University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon E","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Neurology , University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Krans","sequence":"additional","affiliation":[{"name":"Department of Neurology , University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences , Rush University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4781-6376","authenticated-orcid":false,"given":"Peter K","family":"Todd","sequence":"additional","affiliation":[{"name":"Department of Neurology , University of Michigan, Ann Arbor, MI, USA"},{"name":"Ann Arbor Veterans Administration Healthcare , Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"2023020801010968100_ref1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/brain\/awh683","article-title":"Neuropathology of fragile X-associated tremor\/ataxia syndrome (FXTAS)","volume":"129","author":"Greco","year":"2006","journal-title":"Brain"},{"key":"2023020801010968100_ref2","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1093\/brain\/awf184","article-title":"Neuronal intranuclear inclusions in a new cerebellar tremor\/ataxia syndrome among fragile X carriers","volume":"125","author":"Greco","year":"2002","journal-title":"Brain"},{"key":"2023020801010968100_ref3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.brainres.2018.02.006","article-title":"Repeat-associated non-AUG (RAN) translation and other molecular mechanisms in Fragile X Tremor Ataxia Syndrome","volume":"1693","author":"Glineburg","year":"2018","journal-title":"Brain Res."},{"key":"2023020801010968100_ref4","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.neuron.2013.03.026","article-title":"CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome","volume":"78","author":"Todd","year":"2013","journal-title":"Neuron"},{"key":"2023020801010968100_ref5","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1073\/pnas.1013343108","article-title":"Non-ATG-initiated translation directed by microsatellite expansions","volume":"108","author":"Zu","year":"2011","journal-title":"Proc. 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