DDX1 as a regulatory component of the Drosha microprocessor (WP2942)

Posttranscriptional maturation is a critical step in microRNA (miRNA) biogenesis that determines mature miRNA levels. In addition to core components (Drosha and DGCR8 [DiGeorge syndrome critical region gene 8]) in the microprocessor, regulatory RNA-binding proteins may confer the specificity for recruiting and processing of individual primary miRNAs (pri-miRNAs). Here, we identify DDX1 as a regulatory protein that promotes the expression of a subset of miRNAs, including five members in the microRNA-200 (miR-200) family and four miRNAs in an eight-miRNA signature of a mesenchymal ovarian cancer subtype. A majority of DDX1-dependent miRNAs are induced after DNA damage. This induction is facilitated by the ataxia telangiectasia mutated (ATM)-mediated phosphorylation of DDX1. Inhibiting DDX1 promotes ovarian tumor growth and metastasis in a syngeneic mouse model. Analysis of The Cancer Genome Atlas (TCGA) reveals that low DDX1 levels are associated with poor clinical outcome in patients with serous ovarian cancer. These findings suggest that DDX1 is a key modulator in miRNA maturation and ovarian tumor suppression. This pathway is based on the graphical abstract from http://www.cell.com/cell-reports/abstract/S2211-1247(14)00660-3. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2942 CPTAC Assay Portal]
last edited

Authors

Khanspers, Susan, and MaintBot

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: regulatory pathway

Participants

Label Type Compact Identifier
ATM GeneProduct ensembl:ENSG00000149311
DDX1 GeneProduct ensembl:ENSG00000079785
NBN GeneProduct ensembl:ENSG00000104320
DGCR8 GeneProduct ensembl:ENSG00000128191
MRE11A GeneProduct ensembl:ENSG00000020922
RAD50 GeneProduct ensembl:ENSG00000113522
DROSHA GeneProduct ensembl:ENSG00000113360
DDX1 GeneProduct ensembl:ENSG00000079785
DDX1 GeneProduct ensembl:ENSG00000079785

References

  1. Han C, Liu Y, Wan G, Choi HJ, Zhao L, Ivan C, et al. The RNA-binding protein DDX1 promotes primary microRNA maturation and inhibits ovarian tumor progression. Cell Rep. 2014 Sep 11;8(5):1447–60. PubMed Europe PMC Scholia