2. Academic Validation
  3. Structure of Human DROSHA

Structure of Human DROSHA

  • Cell. 2016 Jan 14;164(1-2):81-90. doi: 10.1016/j.cell.2015.12.019.
S Chul Kwon 1,  Tuan Anh Nguyen 1,  Yeon-Gil Choi 1,  Myung Hyun Jo 2,  Sungchul Hohng 3,  V Narry Kim 4,  Jae-Sung Woo 5
Affiliations

Affiliations

  • 1 Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea.
  • 2 Department of Physics and Astronomy, Seoul National University, Seoul 08826, Korea; National Center for Creative Research Initiatives, Seoul National University, Seoul 08826, Korea; Institute of Applied Physics, Seoul National University, Seoul 08826, Korea.
  • 3 Department of Physics and Astronomy, Seoul National University, Seoul 08826, Korea; National Center for Creative Research Initiatives, Seoul National University, Seoul 08826, Korea; Institute of Applied Physics, Seoul National University, Seoul 08826, Korea; Department of Biophysics and Chemical Biology, Seoul National University, Seoul 08826, Korea.
  • 4 Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea. Electronic address: [email protected].
  • 5 Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea. Electronic address: [email protected].
PMID: 26748718 DOI: 10.1016/j.cell.2015.12.019
Abstract

MicroRNA maturation is initiated by RNase III DROSHA that cleaves the stem loop of primary MicroRNA. DROSHA functions together with its cofactor DGCR8 in a heterotrimeric complex known as Microprocessor. Here, we report the X-ray structure of DROSHA in complex with the C-terminal helix of DGCR8. We find that DROSHA contains two DGCR8-binding sites, one on each RNase III domain (RIIID), which mediate the assembly of Microprocessor. The overall structure of DROSHA is surprisingly similar to that of Dicer despite no sequence homology apart from the C-terminal part, suggesting that DROSHA may have evolved from a Dicer homolog. DROSHA exhibits unique features, including non-canonical zinc-finger motifs, a long insertion in the first RIIID, and the kinked link between Connector helix and RIIID, which explains the 11-bp-measuring "ruler" activity of DROSHA. Our study implicates the evolutionary origin of DROSHA and elucidates the molecular basis of Microprocessor assembly and primary MicroRNA processing.

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