Posttranscriptional crossregulation between Drosha and DGCR8.
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.
Han
Jinju
J
School of Biological Sciences and National Creative Research Center, Seoul National University, Seoul 151-742, Korea.
Pedersen
Jakob S
JS
Kwon
S Chul
SC
Belair
Cassandra D
CD
Kim
Young-Kook
YK
Yeom
Kyu-Hyeon
KH
Yang
Woo-Young
WY
Haussler
David
D
Blelloch
Robert
R
Kim
V Narry
VN
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
C474043:DGCR8 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; C517918:DROSHA protein, human; D043244:Ribonuclease III