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dc.contributor.authorKlec, Christiane
dc.contributor.authorKnutsen, Erik
dc.contributor.authorSchwarzenbacher, Daniela
dc.contributor.authorJonas, Katharina
dc.contributor.authorPasculli, Barbara
dc.contributor.authorHeitzer, Ellen
dc.contributor.authorRinner, Beate
dc.contributor.authorKrajina, Katarina
dc.contributor.authorPrinz, Felix
dc.contributor.authorGottschalk, Benjamin
dc.contributor.authorUlz, Peter
dc.contributor.authorDeutsch, Alexander
dc.contributor.authorProkesch, Andreas
dc.contributor.authorJahn, Stephan W.
dc.contributor.authorLellahi, Seyed Mohammad
dc.contributor.authorPerander, Maria
dc.contributor.authorBarbano, Raffaela
dc.contributor.authorGraier, Wolfgang F.
dc.contributor.authorParrella, Paola
dc.contributor.authorCalin, George Adrian
dc.contributor.authorPichler, Martin
dc.description.abstractThe RNA-binding protein ALYREF (THOC4) is involved in transcriptional regulation and nuclear mRNA export, though its role and molecular mode of action in breast carcinogenesis are completely unknown. Here, we identifed high ALYREF expression as a factor for poor survival in breast cancer patients. ALYREF signifcantly infuenced cellular growth, apoptosis and mitochondrial energy metabolism in breast cancer cells as well as breast tumorigenesis in orthotopic mouse models. Transcriptional profling, phenocopy and rescue experiments identifed the short isoform of the lncRNA NEAT1 as a molecular trigger for ALYREF efects in breast cancer. Mechanistically, we found that ALYREF binds to the NEAT1 promoter region to enhance the global NEAT1 transcriptional activity. Importantly, by stabilizing CPSF6, a protein that selectively activates the post-transcriptional generation of the short isoform of NEAT1, as well as by direct binding and stabilization of the short isoform of NEAT1, ALYREF selectively fne-tunes the expression of the short NEAT1 isoform. Overall, our study describes ALYREF as a novel factor contributing to breast carcinogenesis and identifes novel molecular mechanisms of regulation the two isoforms of NEAT1.en_US
dc.identifier.citationKlec, Knutsen, Schwarzenbacher, Jonas, Pasculli, Heitzer, Rinner, Krajina, Prinz, Gottschalk, Ulz, Deutsch, Prokesch, Jahn, Lellahi, Perander, Barbano, Graier, Parrella, Calin, Pichler. ALYREF, a novel factor involved in breast carcinogenesis, acts through transcriptional and post-transcriptional mechanisms selectively regulating the short NEAT1 isoform. Cellular and Molecular Life Sciences (CMLS). 2022;79(7)en_US
dc.identifier.cristinIDFRIDAID 2056536
dc.relation.journalCellular and Molecular Life Sciences (CMLS)
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleALYREF, a novel factor involved in breast carcinogenesis, acts through transcriptional and post-transcriptional mechanisms selectively regulating the short NEAT1 isoformen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US

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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)