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Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation.

Here we identify a component of the nuclear RNA cap-binding complex (CBC), Ars2, that is important for miRNA biogenesis and critical for cell proliferation. Unlike other components of the CBC, Ars2 expression is linked to the proliferative state of the cell. Deletion of Ars2 is developmentally lethal, and deletion in adult mice led to bone marrow failure whereas parenchymal organs composed of nonproliferating cells were unaffected. Depletion of Ars2 or CBP80 from proliferating cells impaired miRNA-mediated repression and led to alterations in primary miRNA processing in the nucleus. Ars2 depletion also reduced the levels of several miRNAs, including miR-21, let-7, and miR-155, that are implicated in cellular transformation. These findings provide evidence for a role for Ars2 in RNA interference regulation during cell proliferation.

Pubmed ID: 19632182

Authors

  • Gruber JJ
  • Zatechka DS
  • Sabin LR
  • Yong J
  • Lum JJ
  • Kong M
  • Zong WX
  • Zhang Z
  • Lau CK
  • Rawlings J
  • Cherry S
  • Ihle JN
  • Dreyfuss G
  • Thompson CB

Journal

Cell

Publication Data

July 23, 2009

Associated Grants

  • Agency: NCI NIH HHS, Id: K01 CA098092
  • Agency: NCI NIH HHS, Id: K01 CA098092-01A2
  • Agency: NCI NIH HHS, Id: K01 CA098092-02
  • Agency: NCI NIH HHS, Id: K01 CA098092-03
  • Agency: NCI NIH HHS, Id: K01 CA098092-04
  • Agency: NCI NIH HHS, Id: K01 CA098092-05
  • Agency: NCI NIH HHS, Id: K01 CA098092-06
  • Agency: NCI NIH HHS, Id: R01 CA092660
  • Agency: NCI NIH HHS, Id: R01 CA092660-09
  • Agency: NCI NIH HHS, Id: R01 CA099179
  • Agency: NCI NIH HHS, Id: R01 CA099179-07
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Arsenic
  • Cell Line
  • Cell Proliferation
  • Guanosine
  • Humans
  • Mice
  • MicroRNAs
  • Nuclear Cap-Binding Protein Complex
  • Nuclear Proteins
  • RNA Interference