Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing

被引：183

作者：

Yeom, Kyu-Hyeon

Lee, Yoontae

Han, Jinju

Suh, Mi Ra

Kim, V. Narry ^{[1
]}

机构：

[1] Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea

[2] Seoul Natl Univ, Res Ctr Funct Cellul, Seoul 151742, South Korea

来源：

NUCLEIC ACIDS RESEARCH | 2006年 / 34卷 / 16期

关键词：

D O I：

10.1093/nar/gkl458

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DGCR8/Pasha is an essential cofactor for Drosha, a nuclear RNase III that cleaves the local hairpin structures embedded in long primary microRNA transcripts (pri-miRNAs) in eukaryotes. Although our knowledge of pri-miRNA processing has significantly advanced in recent years, the precise role of DGCR8 in this pathway remains unclear. In our present study, we dissect the domains in DGCR8 that contribute to the processing of pri-miRNAs and the subcellular localization of DGCR8. Drosha is stabilized through an interaction between its middle domain and the conserved C-terminal domain of DGCR8. Furthermore, DGCR8, but not Drosha, can directly and stably interact with pri-miRNAs, and the tandem dsRNA-binding domains (dsRBDs) in DGCR8 are responsible for this recognition. Moreover, the DGCR8 N-terminal region upstream of its dsRBDs is unnecessary for pri-miRNA processing but is critical for nuclear localization. Our study thus provides further insights into the mechanism of action of the Drosha-DGCR8 complex in pri-miRNA processing.

引用

收藏

页码：4622 / 4629

页数：8

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