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

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

Fareh, M. (TU Delft BN/Chirlmin Joo Lab; Kavli institute of nanoscience Delft)
Yeom, K.H. (TU Delft BN/Chirlmin Joo Lab; Kavli institute of nanoscience Delft)
van Eijkeren-Haagsma, A.C. (TU Delft BN/Technici en Analisten; Kavli institute of nanoscience Delft)
Chauhan, S. (TU Delft BN/Chirlmin Joo Lab; Kavli institute of nanoscience Delft)
Heo, I. (TU Delft BN/Chirlmin Joo Lab; Kavli institute of nanoscience Delft)
Joo, C. (TU Delft BN/Chirlmin Joo Lab; Kavli institute of nanoscience Delft)

2016-12-09

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.

http://resolver.tudelft.nl/uuid:a3c9729b-b070-453f-afa9-8991905c10c6

https://doi.org/10.1038/ncomms13694

2041-1723

Nature Communications, 7, 1-11

Institutional Repository

journal article

© 2016 M. Fareh, K.H. Yeom, A.C. van Eijkeren-Haagsma, S. Chauhan, I. Heo, C. Joo