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Despite the efficacy of current treatments, hepatitis B virus (HBV) cannot be fully eradicated due to the persistence of its minichromosome, or covalently closed circular DNA (cccDNA). The HBV community is investing large human and financial resources to develop new therapeutic strategies that either silence or ideally degrade cccDNA, to cure HBV completely or functionally. cccDNA transcription is considered to be the key step for HBV replication. Transcription not only influences the levels of viral RNA produced, but also directly impacts their quality, generating multiple variants. Growing evidence advocates for the role of the co-transcriptional regulation of HBV RNAs during CHB and viral replication, paving the way for the development of novel therapies targeting these processes. This review focuses on the mechanisms controlling the different co-transcriptional processes that HBV RNAs undergo, and their contribution to both viral replication and HBV-induced liver pathogenesis.<\/jats:p>","DOI":"10.3390\/v16040615","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T08:41:06Z","timestamp":1713256866000},"page":"615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Co-Transcriptional Regulation of HBV Replication: RNA Quality Also Matters"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0700-8403","authenticated-orcid":false,"given":"Guillaume","family":"Giraud","sequence":"first","affiliation":[{"name":"INSERM U1052, CNRS UMR5286, Centre de Recherche en Canc\u00e9rologie de Lyon, Universit\u00e9 Claude Bernard Lyon 1, 69008 Lyon, France"},{"name":"The Lyon Hepatology Institute EVEREST, 69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0017-5316","authenticated-orcid":false,"given":"Khadija","family":"El Achi","sequence":"additional","affiliation":[{"name":"INSERM U1052, CNRS UMR5286, Centre de Recherche en Canc\u00e9rologie de Lyon, Universit\u00e9 Claude Bernard Lyon 1, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2245-0083","authenticated-orcid":false,"given":"Fabien","family":"Zoulim","sequence":"additional","affiliation":[{"name":"INSERM U1052, CNRS UMR5286, Centre de Recherche en Canc\u00e9rologie de Lyon, Universit\u00e9 Claude Bernard Lyon 1, 69008 Lyon, France"},{"name":"The Lyon Hepatology Institute EVEREST, 69003 Lyon, France"},{"name":"Hospices Civils de Lyon, H\u00f4pital Croix Rousse, Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5588-5465","authenticated-orcid":false,"given":"Barbara","family":"Testoni","sequence":"additional","affiliation":[{"name":"INSERM U1052, CNRS UMR5286, Centre de Recherche en Canc\u00e9rologie de Lyon, Universit\u00e9 Claude Bernard Lyon 1, 69008 Lyon, France"},{"name":"The Lyon Hepatology Institute EVEREST, 69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). 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