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.
Crystal structure of human DGCR8 core. Publishing Authors By Initials
Crystal structure of human DGCR8 core. Journal Published:
PUBLICATION TYPE: Research Support, Non-U.S. Gov
Journal: Nature structural & molecular biology
VOLUME: 14
Page Numbers: 847-53
Journal Abbreviation: Nat. Struct. Mol. Biol.
ISSN: 1545-9993
DAY: 19
MONTH: 08
YEAR: 2007
Crystal structure of human DGCR8 core. Information
Number of References:
LANGUAGE: eng
NlmUniqueID: 101186374
Crystal structure of human DGCR8 core. Keywords Mesh Terms:
KEYWORDS: Proteins
MESH TERMS: metabolism
Chemical & Substance for Abstract: Crystal structure of human DGCR8 core. Information
Substance Name: Proteins
Registry Number: 0
Grant and Affiliation Information for Crystal structure of human DGCR8 core.
AFFILIATION: National Creative Research Center for Structural Biology and Department of Life Science, Pohang University of Science and Technology, Hyo-ja dong, San31, Pohang, KyungBook 790-784, South Korea.
Country: United States
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MEDLINETA: Nat Struct Mol Biol
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ACCESSION NUMBER: 2YT4
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