{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:57:13Z","timestamp":1792130233247,"version":"4.4.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"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":["R01NS081366"],"award-info":[{"award-number":["R01NS081366"]}],"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":["R01NS121038"],"award-info":[{"award-number":["R01NS121038"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Frataxin deficiency in Friedreich\u2019s ataxia results from transcriptional downregulation of the FXN gene caused by expansion of the intronic trinucleotide guanine-adenine-adenine (GAA) repeats. We used multiple transcriptomic approaches to determine the molecular mechanism of transcription inhibition caused by long GAAs. We uncovered that transcription of FXN in patient cells is prematurely terminated upstream of the expanded repeats leading to the formation of a novel, truncated and stable RNA. This FXN early terminated transcript (FXN-ett) undergoes alternative, non-productive splicing and does not contribute to the synthesis of functional frataxin. The level the FXN-ett RNA directly correlates with the length of the longer of the two expanded GAA tracts. Targeting GAAs with antisense oligonucleotides or excision of the repeats eliminates the transcription impediment, diminishes expression of the aberrant FXN-ett, while increasing levels of FXN mRNA and frataxin. Non-productive transcription may represent a common phenomenon and attractive therapeutic target in diseases caused by repeat-mediated transcription aberrations.<\/jats:p>","DOI":"10.1093\/hmg\/ddac134","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T14:05:31Z","timestamp":1655388331000},"page":"3539-3557","source":"Crossref","is-referenced-by-count":22,"title":["Premature transcription termination at the expanded GAA repeats and aberrant alternative polyadenylation contributes to the<i>Frataxin<\/i>transcriptional deficit in Friedreich\u2019s ataxia"],"prefix":"10.1093","volume":"31","author":[{"given":"Yanjie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics , University of Alabama at Birmingham, 1825 University Blvd., Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jixue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics , University of Alabama at Birmingham, 1825 University Blvd., Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics , University of Alabama at Birmingham, 1825 University Blvd., Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics , University of Alabama at Birmingham, 1825 University Blvd., Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Giles","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics , University of Alabama at Birmingham, 1825 University Blvd., Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thazha P","family":"Prakash","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals Inc. , 2855 Gazelle Court, Carlsbad, CA 92010 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Rigo","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals Inc. , 2855 Gazelle Court, Carlsbad, CA 92010 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill S","family":"Napierala","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics , University of Alabama at Birmingham, 1825 University Blvd., Birmingham, AL 35294 , USA"},{"name":"Department of Neurology , University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-0641","authenticated-orcid":false,"given":"Marek","family":"Napierala","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics , University of Alabama at Birmingham, 1825 University Blvd., Birmingham, AL 35294 , USA"},{"name":"Department of Neurology , University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"2022101308093083200_ref1","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion","volume":"271","author":"Campuzano","year":"1996","journal-title":"Science"},{"key":"2022101308093083200_ref2","doi-asserted-by":"crossref","first-page":"104606","DOI":"10.1016\/j.nbd.2019.104606","article-title":"Friedreich ataxia- pathogenesis and implications for therapies","volume":"132","author":"Delatycki","year":"2019","journal-title":"Neurobiol. 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