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RNA and DNA G-quadruplexes bind to human dicer and inhibit its activity

Cellular and Molecular Life Sciences, ISSN: 1420-9071, Vol: 78, Issue: 7, Page: 3709-3724
2021
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Article Description

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.

Bibliographic Details

Koralewska, Natalia; Szczepanska, Agnieszka; Ciechanowska, Kinga; Wojnicka, Marta; Pokornowska, Maria; Milewski, Marek C; Gudanis, Dorota; Baranowski, Daniel; Nithin, Chandran; Bujnicki, Janusz M; Gdaniec, Zofia; Figlerowicz, Marek; Kurzynska-Kokorniak, Anna

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Neuroscience

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