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

Author

Listed:
  • Mohamed Fareh

    (Kavli Institute of NanoScience, Delft University of Technology
    Delft University of Technology)

  • Kyu-Hyeon Yeom

    (Kavli Institute of NanoScience, Delft University of Technology
    Delft University of Technology
    Present address: Microbiology, Immunology, and Molecular Genetics, MacDonald Research Laboratories, University of California, Los Angeles, CA 90095-1662, USA)

  • Anna C. Haagsma

    (Kavli Institute of NanoScience, Delft University of Technology
    Delft University of Technology)

  • Sweeny Chauhan

    (Kavli Institute of NanoScience, Delft University of Technology
    Delft University of Technology)

  • Inha Heo

    (Kavli Institute of NanoScience, Delft University of Technology
    Delft University of Technology
    Present address: Hubrecht Institute, 3584CT Utrecht, The Netherlands)

  • Chirlmin Joo

    (Kavli Institute of NanoScience, Delft University of Technology
    Delft University of Technology)

Abstract

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.

Suggested Citation

  • Mohamed Fareh & Kyu-Hyeon Yeom & Anna C. Haagsma & Sweeny Chauhan & Inha Heo & Chirlmin Joo, 2016. "TRBP ensures efficient Dicer processing of precursor microRNA in RNA-crowded environments," Nature Communications, Nature, vol. 7(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13694
    DOI: 10.1038/ncomms13694
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