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TRBP ensures efficient Dicer processing of precursor microRNA in RNA-crowded environments.

Fareh, Mohamed; Yeom, Kyu-Hyeon; Haagsma, Anna C; Chauhan, Sweeny; Heo, Inha; Joo, Chirlmin.
Nat Commun; 7: 13694, 2016 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-27934859
The RNA-binding protein TRBP is a central component of the Dicer complex. Despite a decade of biochemical and structural studies, the essential functionality of TRBP in microRNA (miRNA) biogenesis remains unknown. Here we show that TRBP is an integral cofactor for time-efficient Dicer processing in RNA-crowded environments. We competed for Dicer processing of pre-miRNA with a large amount of cellular RNA species and found that Dicer-TRBP, but not Dicer alone, remains resilient. To apprehend the mechanism of this substrate selectivity, we use single-molecule fluorescence. The real-time observation reveals that TRBP acts as a gatekeeper, precluding Dicer from engaging with pre-miRNA-like substrates. TRBP acquires the selectivity using the PAZ domain of Dicer, whereas Dicer moderates the RNA-binding affinity of TRBP for fast turnover. This coordinated action between TRBP and Dicer accomplishes an efficient way of discarding pre-miRNA-like substrates.
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