title: Posttranscriptional crossregulation between Drosha and DGCR8.
abstract: 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.
authors.affiliation: School of Biological Sciences and National Creative Research Center, Seoul National University, Seoul 151-742, Korea.
authors.forename: Jinju
authors.initials: J
authors.lastname: Han
authors.forename: Jakob S
authors.initials: JS
authors.lastname: Pedersen
authors.forename: S Chul
authors.initials: SC
authors.lastname: Kwon
authors.forename: Cassandra D
authors.initials: CD
authors.lastname: Belair
authors.forename: Young-Kook
authors.initials: YK
authors.lastname: Kim
authors.forename: Kyu-Hyeon
authors.initials: KH
authors.lastname: Yeom
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Yang
authors.forename: David
authors.initials: D
authors.lastname: Haussler
authors.forename: Robert
authors.initials: R
authors.lastname: Blelloch
authors.forename: V Narry
authors.initials: VN
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020871:RNA Stability; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism
chemical_list: C474043:DGCR8 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; C517918:DROSHA protein, human; D043244:Ribonuclease III