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Global dysregulation of circular RNAs in frontal cortex and whole blood from DM1 and DM2

cris.lastimport.scopus2025-10-23T06:59:04Z
cris.lastimport.wos2025-10-23T06:55:03Z
dc.abstract.enMyotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular disorders associated with expansions of microsatellites, respectively, in DMPK and CNBP. Their pathogenesis is linked to the global aberrant alternative splicing (AAS) of many genes and marks mostly muscular and neuronal tissues, while blood is the least affected. Recent data in DM1 skeletal muscles indicated that abnormalities in RNA metabolism also include global upregulation of circular RNAs (circRNAs). CircRNAs are a heterogeneous group considered splicing errors and by-products of canonical splicing. To elucidate whether circRNA dysregulation is an inherent feature of the myotonic environment, we perform their analysis in the frontal cortex and whole blood of DM1 and DM2 patients. We find a global elevation of circRNAs in both tissues, and its magnitude is neither correlated with the differences in their parental gene expression nor is associated with AAS published earlier. Aberrantly spliced cassette exons of linear transcripts affected in DM1 and DM2 are not among the circularized exons, which unique genomic features prerequisite back-splicing. However, the blueprint of the AAS of linear RNAs is found in a variety of circRNA isoforms. The heterogeneity of circRNAs also originates from the utilization of exonic and intronic cryptic donors/acceptors in back splice junctions, and intron-containing circRNAs are more characteristic of the blood. Overall, this study reveals circRNA dysregulation in various tissues from DM1 and DM2; however, their levels do not correlate with the AAS in linear RNAs, suggesting a potential independent regulatory mechanism underlying circRNA upregulation in myotonic dystrophy.
dc.affiliationWydział Rolnictwa, Ogrodnictwa i Bioinżynierii
dc.affiliation.instituteKatedra Biochemii i Biotechnologii
dc.contributor.authorSrinivasan, Arvind
dc.contributor.authorMagner, Dorota
dc.contributor.authorKozłowski, Piotr
dc.contributor.authorPhilips, Anna
dc.contributor.authorKajdasz, Arkadiusz
dc.contributor.authorWojciechowski, Paweł
dc.contributor.authorWojciechowska, Marzena
dc.date.access2025-06-12
dc.date.accessioned2025-06-12T08:32:32Z
dc.date.available2025-06-12T08:32:32Z
dc.date.copyright2025-04-02
dc.date.issued2025
dc.description.abstract<jats:title>Abstract</jats:title> <jats:p>Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular disorders associated with expansions of microsatellites, respectively, in <jats:italic>DMPK</jats:italic> and <jats:italic>CNBP</jats:italic>. Their pathogenesis is linked to the global aberrant alternative splicing (AAS) of many genes and marks mostly muscular and neuronal tissues, while blood is the least affected. Recent data in DM1 skeletal muscles indicated that abnormalities in RNA metabolism also include global upregulation of circular RNAs (circRNAs). CircRNAs are a heterogeneous group considered splicing errors and by-products of canonical splicing. To elucidate whether circRNA dysregulation is an inherent feature of the myotonic environment, we perform their analysis in the frontal cortex and whole blood of DM1 and DM2 patients. We find a global elevation of circRNAs in both tissues, and its magnitude is neither correlated with the differences in their parental gene expression nor is associated with AAS published earlier. Aberrantly spliced cassette exons of linear transcripts affected in DM1 and DM2 are not among the circularized exons, which unique genomic features prerequisite back-splicing. However, the blueprint of the AAS of linear RNAs is found in a variety of circRNA isoforms. The heterogeneity of circRNAs also originates from the utilization of exonic and intronic cryptic donors/acceptors in back splice junctions, and intron-containing circRNAs are more characteristic of the blood. Overall, this study reveals circRNA dysregulation in various tissues from DM1 and DM2; however, their levels do not correlate with the AAS in linear RNAs, suggesting a potential independent regulatory mechanism underlying circRNA upregulation in myotonic dystrophy.</jats:p>
dc.description.accesstimeat_publication
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0,00
dc.description.if3,8
dc.description.number4
dc.description.points100
dc.description.versionfinal_published
dc.description.volume144
dc.identifier.doi10.1007/s00439-025-02729-x
dc.identifier.eissn1432-1203
dc.identifier.issn0340-6717
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/2836
dc.identifier.weblinkhttps://link.springer.com/article/10.1007/s00439-025-02729-x
dc.languageen
dc.relation.ispartofHuman Genetics
dc.relation.pages417-432
dc.rightsCC-BY
dc.sciencecloudsend
dc.share.typeOTHER
dc.subject.encircular RNAs
dc.subject.enmyotonic dystrophy
dc.subject.enback-splicing
dc.subject.encryptic splice sites
dc.subject.enalternative splicing
dc.titleGlobal dysregulation of circular RNAs in frontal cortex and whole blood from DM1 and DM2
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.issue4
oaire.citation.volume144