Journal
CELL
Volume 136, Issue 1, Pages 75-84Publisher
CELL PRESS
DOI: 10.1016/j.cell.2008.10.053
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Funding
- Creative Research Initiatives Program [R16-2007-073-01000-0]
- BK21 Research Fellowships
- Ministry of Education, Science, and Technology of Korea
- Danish Medical Research Council [271-06-0711]
- University of California, San Francisco, Urology Developmental Award
- Prostate Cancer Foundation
- National Institutes of Health [K08 NS48118, RO1 NS057221]
- Stem Cell Research Foundation
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The Drosha-DGCR8 complex, also known as Microprocessor, is essential for microRNA (miRNA) maturation. Drosha functions as the catalytic subunit, while DGCR8 (also known as Pasha) recognizes the RNA substrate. Although the action mechanism of this complex has been intensively studied, it remains unclear how Drosha and DGCR8 are regulated and if these proteins have any additional role(s) apart from miRNA processing. Here, we report that Drosha and DGCR8 regulate each other posttranscriptionally. The Drosha-DGCR8 complex cleaves the hairpin structures embedded in the DGCR8 mRNA and thereby destabilizes the mRNA. We further find that DGCR8 stabilizes the Drosha protein via protein-protein interaction. This crossregulation between Drosha and DGCR8 may contribute to the homeostatic control of miRNA biogenesis. Furthermore, microarray analyses suggest that a number of mRNAs may be downregulated in a Microprocessor-dependent, miRNA-independent manner. Our study reveals a previously unsuspected function of Microprocessor in mRNA stability control.
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