DDX1 as a regulatory component of the Drosha microprocessor (Homo sapiens)

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Description

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.

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Bibliography

  1. Han C, Liu Y, Wan G, Choi HJ, Zhao L, Ivan C, He X, Sood AK, Zhang X, Lu X; ''The RNA-binding protein DDX1 promotes primary microRNA maturation and inhibits ovarian tumor progression.''; Cell Rep, 2014 PubMed

History

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CompareRevisionActionTimeUserComment
94276view17:38, 30 August 2017Khanspersupdated for clarity and added phosphorylation
87380view11:05, 22 July 2016MaintBotadded missing graphids
87223view14:40, 19 July 2016SusanOntology Term : 'regulatory pathway' added !
84388view21:34, 18 February 2016KhanspersModified description
80337view22:31, 5 June 2015KhanspersModified description
80334view22:24, 5 June 2015KhanspersNew pathway

External references

Datanodes

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NameTypeDatabase referenceComment
ATMGeneProductENSG00000149311 (Ensembl)
DDX1GeneProductENSG00000079785 (Ensembl)
DGCR8GeneProductENSG00000128191 (Ensembl)
DROSHAGeneProductENSG00000113360 (Ensembl)
MRE11AGeneProductENSG00000020922 (Ensembl)
NBNGeneProductENSG00000104320 (Ensembl)
RAD50GeneProductENSG00000113522 (Ensembl)

Annotated Interactions

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