Skip to main content
Journal cover image

Rescuing dicer defects via inhibition of an anti-dicing nuclease.

Publication ,  Journal Article
Asada, K; Canestrari, E; Fu, X; Li, Z; Makowski, E; Wu, Y-C; Mito, JK; Kirsch, DG; Baraban, J; Paroo, Z
Published in: Cell Rep
November 20, 2014

Genetic defects in the microRNA (miRNA) generating enzyme, dicer, are increasingly linked to disease. Loss of miRNA in dicer deficiency is thought to be due to loss of miRNA-generating activity. Here, we demonstrate a catabolic mechanism driving miRNA depletion in dicer deficiency. We developed a Dicer-antagonist assay revealing a pre-miRNA degrading enzyme that competes with pre-miRNA processing. We purified this pre-miRNA degrading activity using an unbiased chromatographic procedure and identified the ribonuclease complex Translin/Trax (TN/TX). In wild-type dicer backgrounds, pre-miRNA processing was dominant. However, in dicer-deficient contexts, TN/TX broadly suppressed miRNA. These findings indicate that miRNA depletion in dicer deficiency is due to the combined loss of miRNA-generating activity and catabolic function of TN/TX. Importantly, inhibition of TN/TX mitigated loss of both miRNA and tumor suppression with dicer haploinsufficiency. These studies reveal a potentially druggable target for restoring miRNA function in cancers and emerging dicer deficiencies.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

November 20, 2014

Volume

9

Issue

4

Start / End Page

1471 / 1481

Location

United States

Related Subject Headings

  • Ribonuclease III
  • RNA-Binding Proteins
  • RNA Stability
  • RNA Processing, Post-Transcriptional
  • RNA Precursors
  • Molecular Sequence Data
  • MicroRNAs
  • Mice, Inbred C57BL
  • Humans
  • Hela Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Asada, K., Canestrari, E., Fu, X., Li, Z., Makowski, E., Wu, Y.-C., … Paroo, Z. (2014). Rescuing dicer defects via inhibition of an anti-dicing nuclease. Cell Rep, 9(4), 1471–1481. https://doi.org/10.1016/j.celrep.2014.10.021
Asada, Ken, Emanuele Canestrari, Xiuping Fu, Zhi Li, Edward Makowski, Yen-Ching Wu, Jeffrey K. Mito, David G. Kirsch, Jay Baraban, and Zain Paroo. “Rescuing dicer defects via inhibition of an anti-dicing nuclease.Cell Rep 9, no. 4 (November 20, 2014): 1471–81. https://doi.org/10.1016/j.celrep.2014.10.021.
Asada K, Canestrari E, Fu X, Li Z, Makowski E, Wu Y-C, et al. Rescuing dicer defects via inhibition of an anti-dicing nuclease. Cell Rep. 2014 Nov 20;9(4):1471–81.
Asada, Ken, et al. “Rescuing dicer defects via inhibition of an anti-dicing nuclease.Cell Rep, vol. 9, no. 4, Nov. 2014, pp. 1471–81. Pubmed, doi:10.1016/j.celrep.2014.10.021.
Asada K, Canestrari E, Fu X, Li Z, Makowski E, Wu Y-C, Mito JK, Kirsch DG, Baraban J, Paroo Z. Rescuing dicer defects via inhibition of an anti-dicing nuclease. Cell Rep. 2014 Nov 20;9(4):1471–1481.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

November 20, 2014

Volume

9

Issue

4

Start / End Page

1471 / 1481

Location

United States

Related Subject Headings

  • Ribonuclease III
  • RNA-Binding Proteins
  • RNA Stability
  • RNA Processing, Post-Transcriptional
  • RNA Precursors
  • Molecular Sequence Data
  • MicroRNAs
  • Mice, Inbred C57BL
  • Humans
  • Hela Cells