{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:00:19Z","timestamp":1767891619302,"version":"3.49.0"},"reference-count":65,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academic leadership program Priority 2030 proposed by Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is a neurodegenerative disorder caused by the expansion of the CAG repeat in exon 1 of the HTT gene, leading to the formation of a toxic variant of the huntingtin protein. It is a rare but severe hereditary disease for which no effective treatment method has been found yet. The primary therapeutic targets include the mutant protein and the mutant mRNA of HTT. Current clinical trial approaches in gene therapy involve the application of splice modulation, siRNA, or antisense oligonucleotides for RNA-targeted knockdown of HTT. However, these approaches do not take into account the diversity of HTT transcript isoforms in the normal conditions and in HD. In this review, we discuss the features of transcriptional regulation and processing that lead to the formation of various HTT mRNA variants, each of which may uniquely contribute to the progression of the disease. Furthermore, understanding the role of known transcription factors of HTT in pathology may aid in the development of potentially new therapeutic tools based on endogenous regulators.<\/jats:p>","DOI":"10.3390\/ijms252111493","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T04:15:02Z","timestamp":1730088902000},"page":"11493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Regulation of HTT mRNA Biogenesis: The Norm and Pathology"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3117-0317","authenticated-orcid":false,"given":"Alexandra E.","family":"Zubkova","sequence":"first","affiliation":[{"name":"Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya Str., 8\/2, Moscow 119048, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8940-9173","authenticated-orcid":false,"given":"Dmitry V.","family":"Yudkin","sequence":"additional","affiliation":[{"name":"Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya Str., 8\/2, Moscow 119048, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/mds.29228","article-title":"Prevalence and incidence of Huntington\u2019s disease: An updated systematic review and meta-analysis","volume":"37","author":"Medina","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1159\/000524732","article-title":"Epidemiology of Huntington\u2019s disease in the United States medicare and medicaid populations","volume":"56","author":"Exuzides","year":"2022","journal-title":"Neuroepidemiology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jiang, A., Handley, R.R., Lehnert, K., and Snell, R.G. 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