Quaking isoforms cooperate to promote the mesenchymal phenotype

Daniel P. Neumann, Caroline A. Phillips, Rachael Lumb, Helen M. Palethorpe, Yesha Ramani, Brett G. Hollier, Luke A. Selth, Cameron P. Bracken, Gregory J. Goodall, Philip A. Gregory

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The 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 used 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.

Original languageEnglish
Article numberar17
Number of pages12
JournalMolecular Biology of the Cell
Issue number2
Early online date12 Jan 2024
Publication statusPublished - 1 Feb 2024


  • RNA-binding proteins
  • Quaking (QKI)
  • Phenotypes
  • Isoforms


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