2. Academic Validation
  3. Functional Anatomy of the Human Microprocessor

Functional Anatomy of the Human Microprocessor

  • Cell. 2015 Jun 4;161(6):1374-87. doi: 10.1016/j.cell.2015.05.010.
Tuan Anh Nguyen 1,  Myung Hyun Jo 2,  Yeon-Gil Choi 1,  Joha Park 1,  S Chul Kwon 1,  Sungchul Hohng 3,  V Narry Kim 4,  Jae-Sung Woo 5
Affiliations

Affiliations

  • 1 Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
  • 2 Department of Physics and Astronomy, Seoul National University, Seoul 151-742, Korea; National Center for Creative Research Initiatives, Seoul National University, Seoul 151-742, Korea; Institute of Applied Physics, Seoul National University, Seoul 151-742, Korea.
  • 3 Department of Physics and Astronomy, Seoul National University, Seoul 151-742, Korea; National Center for Creative Research Initiatives, Seoul National University, Seoul 151-742, Korea; Institute of Applied Physics, Seoul National University, Seoul 151-742, Korea; Department of Biophysics and Chemical Biology, Seoul National University, Seoul 151-742, Korea.
  • 4 Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea. Electronic address: [email protected].
  • 5 Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea. Electronic address: [email protected].
PMID: 26027739 DOI: 10.1016/j.cell.2015.05.010
Abstract

MicroRNA (miRNA) maturation is initiated by Microprocessor composed of RNase III DROSHA and its cofactor DGCR8, whose fidelity is critical for generation of functional miRNAs. To understand how Microprocessor recognizes pri-miRNAs, we here reconstitute human Microprocessor with purified recombinant proteins. We find that Microprocessor is an ∼364 kDa heterotrimeric complex of one DROSHA and two DGCR8 molecules. Together with a 23-amino acid peptide from DGCR8, DROSHA constitutes a minimal functional core. DROSHA serves as a "ruler" by measuring 11 bp from the basal ssRNA-dsRNA junction. DGCR8 interacts with the stem and apical elements through its dsRNA-binding domains and RNA-binding heme domain, respectively, allowing efficient and accurate processing. DROSHA and DGCR8, respectively, recognize the basal UG and apical UGU motifs, which ensure proper orientation of the complex. These findings clarify controversies over the action mechanism of DROSHA and allow us to build a general model for pri-miRNA processing.

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