Quaking isoforms cooperate to promote the mesenchymal phenotype

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dc.contributor.authorNeumann, D.P.
dc.contributor.authorPhillips, C.A.
dc.contributor.authorLumb, R.
dc.contributor.authorPalethorpe, H.M.
dc.contributor.authorRamani, Y.
dc.contributor.authorHollier, B.G.
dc.contributor.authorSelth, L.A.
dc.contributor.authorBracken, C.P.
dc.contributor.authorGoodall, G.J.
dc.contributor.authorGregory, P.A.
dc.contributor.editorCorbett, A.
dc.date.issued2024
dc.description.abstractThe RNA-binding protein Quaking (QKI) has widespread effects on mRNA regulation including alternative splicing, stability, translation, and localization of target mRNAs. Recently, QKI was found to be induced during epithelial-mesenchymal transition (EMT), where it promotes a mesenchymal alternative splicing signature that contributes to the mesenchymal phenotype. QKI is itself alternatively spliced to produce three major isoforms, QKI-5, QKI-6, and QKI-7. While QKI-5 is primarily localized to the nucleus where it controls mesenchymal splicing during EMT, the functions of the two predominantly cytoplasmic isoforms, QKI-6, and QKI-7, in this context remain uncharacterized. Here we employed CRISPR-mediated depletion of QKI in a human mammary epithelial cell model of EMT and studied the effects of expressing the QKI isoforms in isolation and in combination. QKI-5 was required to induce mesenchymal morphology, while combined expression of QKI-5 with either QKI-6 or QKI-7 further enhanced mesenchymal morphology and cell migration. In addition, we found that QKI-6 and QKI-7 can partially localize to the nucleus and contribute to alternative splicing of QKI target genes. These findings indicate that the QKI isoforms function in a dynamic and cooperative manner to promote the mesenchymal phenotype.
dc.description.statementofresponsibilityDaniel P. Neumann, Caroline A. Phillips, Rachael Lumb, Helen M. Palethorpe, Yesha Ramani, Brett G. Hollier, Luke A. Selth, Cameron P. Bracken, Gregory J. Goodall, and Philip A. Gregory
dc.identifier.citationMolecular Biology of the Cell, 2024; 35(2):ar17-1-ar17-12
dc.identifier.doi10.1091/mbc.E23-08-0316
dc.identifier.issn1059-1524
dc.identifier.issn1939-4586
dc.identifier.orcidSelth, L.A. [0000-0002-4686-1418]
dc.identifier.orcidGoodall, G.J. [0000-0003-1294-0692]
dc.identifier.orcidGregory, P.A. [0000-0002-0999-0632]
dc.identifier.urihttps://hdl.handle.net/2440/143490
dc.language.isoen
dc.publisherAmerican Society for Cell Biology (ASCB)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1128479
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1164669
dc.rights© 2024 Neumann et al. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution 4.0 International Creative Commons CC-BY 4.0 License (https:// creativecommons.org/licenses/by/4.0/).
dc.source.urihttp://dx.doi.org/10.1091/mbc.e23-08-0316
dc.subjectQuaking isoforms
dc.subject.meshHumans
dc.subject.meshProtein Isoforms
dc.subject.meshRNA, Messenger
dc.subject.meshRNA Splicing
dc.subject.meshAlternative Splicing
dc.subject.meshPhenotype
dc.titleQuaking isoforms cooperate to promote the mesenchymal phenotype
dc.typeJournal article
pubs.publication-statusPublished

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