Crystal structure of human DGCR8 core
- 19 August 2007
- journal article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 14 (9), 847-853
- https://doi.org/10.1038/nsmb1294
Abstract
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.Keywords
This publication has 40 references indexed in Scilit:
- Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processingNucleic Acids Research, 2006
- Molecular Basis for the Recognition of Primary microRNAs by the Drosha-DGCR8 ComplexCell, 2006
- Structural Insight into the Mechanism of Double-Stranded RNA Processing by Ribonuclease IIICell, 2006
- MicroRNA biogenesis: coordinated cropping and dicingNature Reviews Molecular Cell Biology, 2005
- The Drosha-DGCR8 complex in primary microRNA processingGenes & Development, 2004
- The double-stranded-RNA-binding motif: interference and much moreNature Reviews Molecular Cell Biology, 2004
- The Microprocessor complex mediates the genesis of microRNAsNature, 2004
- Processing of primary microRNAs by the Microprocessor complexNature, 2004
- A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNAScience, 2001
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997