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.