1. RNA and DNA G-quadruplexes bind to human Dicer and inhibit its activity
- Author
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Janusz M. Bujnicki, Marek Figlerowicz, Dorota Gudanis, Chandran Nithin, Marek C. Milewski, Daniel Baranowski, Agnieszka Szczepanska, Kinga Ciechanowska, Maria Pokornowska, Natalia Koralewska, Marta Wojnicka, Anna Kurzynska-Kokorniak, and Zofia Gdaniec
- Subjects
Genome instability ,Dicer PPC cassette ,Ribonuclease III ,Protein Conformation ,MiRNA biogenesis ,G-quadruplex ,DEAD-box RNA Helicases ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Transcription (biology) ,microRNA ,Humans ,heterocyclic compounds ,Dicer inhibition ,Enzyme Inhibitors ,Molecular Biology ,030304 developmental biology ,Ribonucleoprotein complexes ,Pharmacology ,0303 health sciences ,biology ,Chemistry ,030302 biochemistry & molecular biology ,fungi ,DNA replication ,RNA ,food and beverages ,Cell Biology ,DNA ,Cell biology ,Regulation of enzyme activity ,PAZ domain ,G-Quadruplexes ,MicroRNAs ,biology.protein ,Molecular Medicine ,Nucleic Acid Conformation ,Original Article ,Dicer - Abstract
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. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-03795-w.
- Published
- 2020
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