The Drosha-DGCR8 complex in primary microRNA processing.

By Jinju Han, Yoontae Lee, Kyu‐Hyun Yeom, Young‐Kook Kim, Hua Jin, V. Narry Kim. Genes & Development, 2004

2,338 citations recorded by the source corpus.

RNase III proteins play key roles in microRNA (miRNA) biogenesis. The nuclear RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic RNase III Dicer to generate mature miRNAs. While Dicer (class III) and other simple RNase III proteins (class I) have been studied intensively, the class II enzyme Drosha remains to be characterized. Here we dissected the action mechanism of human Drosha by generating mutants and by characterizing its new interacting partner, DGCR8. The basic action mechanism of Drosha was found to be similar to that of human Dicer; the RNase III domains A and B form an intramolecular dimer and cleave the 3' and 5' strands of the stem, respectively. Human Drosha fractionates at approximately 650 kDa, indicating that Drosha functions as a large complex. In this complex, Drosha interacts with DGCR8, which contains two double-stranded RNA (dsRNA)-binding domains. By RNAi and biochemical reconstitution, we show that DGCR8 may be an essential component of the pri-miRNA processing complex, along with Drosha. Based on these results, we propose a model for the action mechanism of class II RNase III proteins.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0ba886df565b1507d04ca9c0d546268ee5a0b475

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Citations in the corpus

microRNAs in cancer (2013, background): “The mature miRNA is first cropped in the nucleus by the nuclear Drosha/DGCR8 heterodimer, which cleaves at the pri-miRNA stem and releases a hairpin-structured pre-miRNA of 60–100 nt (17).”
Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018, background): “This results in the formation of a 2 nt 3 overhang on pre-miRNA (29).”
MicroRNAs in development and disease. (2011, background): “The pri-miRNA is cleaved in the nucleus at the base of the stem-loop structure by the RNAse III enzyme Drosha (344) and its partner DGCR8/Pasha (139, 216, 229, 330) (FIGURE 1), which have been shown to require an intact secondary structure of the pri-miRNA for efficient processing (230).”
Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. (2008, background): “Drosha in a complex with DGCR8/Pasha cleaves a long primary transcript (pri-miRNA) liberating a characteristic hairpin structure (pre-miRNA) (Denli et al., 2004; Gregory et al., 2004; Han et al., 2004; Landthaler et al., 2004; Lee et al., 2003).”
Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. (2009, background): “They are processed cotranscriptionally into pre-miRNAs by the microprocessor that contains an RNase III enzyme called Drosha, and an RNA binding protein, DGCR8 (Lee et al. 2003; Han et al. 2004).”
TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. (2009, background): “In the nucleus, the primary transcript of miRNA gene (pri-miRNA) is cropped into the hairpin-structured precursor (pre-miRNA) by nuclear RNase III Drosha (Lee et al., 2003) and its cofactor DGCR8/Pasha (Denli et al., 2004; Gregory et al., 2004; Han et al., 2004; Landthaler et al., 2004).”
An overview of microRNAs (2015, background): “The RNA binding protein DGCR8 is associated with Drosha and is required for cleavage of the pri-miRNA[39-41].”