2021

Cellular and Molecular Life Sciences

Rocznik: 2021 | Tom: 78 | Numer: 7

artykuł naukowy

angielski

EN 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.

3709 - 3724

10.1007/s00018-021-03795-w

http://link.springer.com/content/pdf/10.1007/s00018-021-03795-w.pdf

CC BY-ND (uznanie autorstwa - bez utworów zależnych)

ostateczna wersja opublikowana

03.2021

przed opublikowaniem

140

140