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Crystal structure of human DGCR8 core

Cited 89 time in Web of Science Cited 96 time in Scopus

Sohn, Sun Young; Bae, Won Jin; Kim, Jeong Joo; Yeom, Kyu-Hyeon; Kim, V. Narry; Cho, Yunje

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Nature Publishing Group
Nature Structural and Molecular Biology, Vol.14 No.9, pp.847-853
A complex of Drosha with DGCR8 ( or its homolog Pasha) cleaves primary microRNA ( pri- miRNA) substrates into precursor miRNA and initiates the microRNA maturation process. Drosha provides the catalytic site for this cleavage, whereas DGCR8 or Pasha provides a frame for anchoring substrate pri- miRNAs. To clarify the molecular basis underlying recognition of pri- miRNA by DGCR8 and Pasha, we determined the crystal structure of the human DGCR8 core ( DGCR8S, residues 493 - 720). In the structure, the two double- stranded RNA - binding domains ( dsRBDs) are arranged with pseudo two- fold symmetry and are tightly packed against the C- terminal helix. The H2 helix in each dsRBD is important for recognition of pri- miRNA substrates. This structure, together with fluorescent resonance energy transfer and mutational analyses, suggests that the DGCR8 core recognizes pri- miRNA in two possible orientations. We propose a model for DGCR8' s recognition of pri- miRNA.
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  • College of Natural Sciences
  • School of Biological Sciences
Research Area Molecular Biology & Genetics


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