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Guanine (G)-rich single-stranded nucleic acids can adopt G-quadruplex structures. Accumulating evidence indicates that G-quadruplexes serve important regulatory roles in fundamental biological processes such as DNA replication, transcription, and translation, while aberrant G-quadruplex formation is linked to genome instability and cancer. Understanding the biological functions played by G-quadruplexes requires detailed knowledge of their protein interactome. Here, we report that both RNA and DNA G-quadruplexes are bound by human Dicer in vitro. Using in vitro binding assays, mutation studies, and computational modeling we demonstrate that G-quadruplexes can interact with the Platform-PAZ-Connector helix cassette of Dicer, the region responsible for anchoring microRNA precursors (pre-miRNAs). Consequently, we show that G-quadruplexes efficiently and stably inhibit the cleavage of pre-miRNA by Dicer. Our data highlight the potential of human Dicer for binding of G-quadruplexes and allow us to propose a G-quadruplex-driven sequestration mechanism of Dicer regulation.

Citation

Natalia Koralewska, Agnieszka Szczepanska, Kinga Ciechanowska, Marta Wojnicka, Maria Pokornowska, Marek C Milewski, Dorota Gudanis, Daniel Baranowski, Chandran Nithin, Janusz M Bujnicki, Zofia Gdaniec, Marek Figlerowicz, Anna Kurzynska-Kokorniak. RNA and DNA G-quadruplexes bind to human dicer and inhibit its activity. Cellular and molecular life sciences : CMLS. 2021 Apr;78(7):3709-3724

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PMID: 33733306

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