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ADAR1 knockout leads to global deregulation of translation and to translational shutdown upon IFN-α/β treatment in human Huh7.5 hepatocytes

dc.contributor.authorRoučová, Kristina
dc.contributor.authorVopálenský, Václav
dc.contributor.authorMašek, Tomáš
dc.contributor.authorProvazník, Jan
dc.contributor.authorLandry, Jonathan
dc.contributor.authorAzevedo, Nayara
dc.contributor.authorEhler, Edvard
dc.contributor.authorBeneš, Vladimír
dc.contributor.authorPospíšek, Martin
dc.date.accessioned2024-12-03T12:10:50Z
dc.date.available2024-12-03T12:10:50Z
dc.date.issued2024
dc.identifier.urihttps://hdl.handle.net/20.500.14178/2732
dc.description.abstractIn recent years, numerous evidence has been accumulated about the extent of A-to-I editing in human RNAs and the key role ADAR1 plays in the cellular editing machinery. It has been shown that A-to-I editing occurrence and frequency are tissue specific and essential for some tissue development, such as liver. Liver and hepatocytes specifically belong to the most affected tissues in ADAR1 KO mice (Hartner JC et al., 2004, J Biol Chem 279: 4894-4902; Wang G et al., 2015, Am J Pathol 185: 3224-3237). To study the effect of ADAR1 function in hepatocytes, we have created Huh7.5 ADAR1 KO cell lines. Upon IFN treatment, the Huh7.5 ADAR1 KO cells show rapid arrest of growth and translation, from which they do not recover. We analyzed translatome changes by employing a method based on sequencing of separate polysome profile RNA fractions. We found significant changes in transcriptome and translatome of the Huh7.5 ADAR1 KO cells. The most prominent changes include global deregulation of translation, negatively affected transcription by RNA polymerase III and changes of snoRNA and Y RNA levels. Furthermore, we observed that ADAR1 KO polysomes are enriched in mRNAs coding for proteins pivotal in a wide range of biological processes such as RNA localization and RNA processing, whereas the unbound fraction is enriched mainly in mRNAs coding for ribosomal proteins and translational factors. All these could also indicate that ADAR1 may play a relevant role in small RNA metabolism and ribosome biogenesis. This work was supported by the project National Institute of Virology and Bacteriology (Programme EXCELES, ID Project No. LX22NPO5103) - Funded by the European Union - Next Generation EU and was recently published in Roucova K. et al., RNA, Published in Advance, June 6, 2024, doi:10.1261/rna.080097.124.en
dc.language.isoen
dc.rightsCreative Commons Uveďte původ 4.0 Internationalcs
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.titleADAR1 knockout leads to global deregulation of translation and to translational shutdown upon IFN-α/β treatment in human Huh7.5 hepatocytesen
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/legalcode
dc.date.updated2024-12-03T12:10:50Z
dc.subject.keywordADAR1en
dc.subject.keywordRNAen
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM//LX22NPO5103
dc.date.embargoStartDate2024-12-03
dc.type.obd110
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.obd655580
dc.subject.rivPrimary10000::10600
dcterms.isPartOf.nameAbstracts of papers presented at the 2024 meeting on TRANSLATIONAL CONTROL
dcterms.isPartOf.journalYear2024
uk.faculty.primaryId115
uk.faculty.primaryNamePřírodovědecká fakultacs
uk.faculty.primaryNameFaculty of Scienceen
uk.faculty.secondaryId117
uk.faculty.secondaryNamePedagogická fakultacs
uk.faculty.secondaryNameFaculty of Educationen
uk.department.primaryId1034
uk.department.primaryNameKatedra genetiky a mikrobiologiecs
uk.department.primaryNameDepartment of Genetics and Microbiologyen
uk.department.secondaryId1569
uk.department.secondaryNameKatedra biologie a environmentálních studiícs
uk.department.secondaryNameDepartment of Biology and Environmental Studiesen
uk.event.nameTranslational Control
dc.description.pageRange275-275
dc.type.obdHierarchyCsABSTRAKT::abstrakt::abstrakt v elektronické podoběcs
dc.type.obdHierarchyEnABSTRACT::abstract::abstract in e-formen
dc.type.obdHierarchyCode110::130::136en
uk.displayTitleADAR1 knockout leads to global deregulation of translation and to translational shutdown upon IFN-α/β treatment in human Huh7.5 hepatocytesen


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