The RNA Binding Protein Quaking Regulates Formation of circRNAs

Simon Conn, Katherine Pillman, John Toubia, Vanessa Conn, Marika Salmanidis, Caroline Phillips, Suraya Roslan, Andreas Schreiber, Philip A Gregory, Gregory Goodall

    Research output: Contribution to journalArticle

    729 Citations (Scopus)

    Abstract

    Circular RNAs (circRNAs), formed by non-sequential back-splicing of pre-mRNA transcripts, are a widespread form of non-coding RNA in animal cells. However, it is unclear whether the majority of circRNAs represent splicing by-products without function or are produced in a regulated manner to carry out specific cellular functions. We show that hundreds of circRNAs are regulated during human epithelial-mesenchymal transition (EMT) and find that the production of over one-third of abundant circRNAs is dynamically regulated by the alternative splicing factor, Quaking (QKI), which itself is regulated during EMT. Furthermore, by modulating QKI levels, we show the effect on circRNA abundance is dependent on intronic QKI binding motifs. Critically, the addition of QKI motifs is sufficient to induce de novo circRNA formation from transcripts that are normally linearly spliced. These findings demonstrate circRNAs are both purposefully synthesized and regulated by cell-type specific mechanisms, suggesting they play specific biological roles in EMT.

    Original languageEnglish
    Pages (from-to)1125-1134
    Number of pages10
    JournalCell
    Volume160
    Issue number6
    DOIs
    Publication statusPublished - 2015

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  • Cite this

    Conn, S., Pillman, K., Toubia, J., Conn, V., Salmanidis, M., Phillips, C., Roslan, S., Schreiber, A., Gregory, P. A., & Goodall, G. (2015). The RNA Binding Protein Quaking Regulates Formation of circRNAs. Cell, 160(6), 1125-1134. https://doi.org/10.1016/j.cell.2015.02.014