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DNA-damage-induced nuclear export of precursor microRNAs is regulated by the ATM-AKT pathway

Guohui Wan1, Xinna Zhang, Robert R Langley

  • 1Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Cell Reports
|June 25, 2013
PubMed

Insights

DNA damage accelerates microRNA (miRNA) nuclear export via ATM-activated AKT signaling, which phosphorylates Nup153. This enhances Exportin-5 interaction, increasing pre-miRNA transport and maturation.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • MicroRNA (miRNA) biogenesis involves transcription and posttranscriptional processing.
  • DNA damage can induce miRNA processing via RNA-binding proteins in Drosha and Dicer complexes.
  • Regulation of nuclear export of pre-miRNAs during DNA damage response is poorly understood.

Purpose of the Study:

  • To investigate the regulation of pre-miRNA nuclear export following DNA damage.
  • To elucidate the role of DNA-damage signaling pathways in miRNA maturation.

Main Methods:

  • Investigated pre-miRNA nuclear export dynamics after DNA damage.
  • Utilized techniques to assess ATM-dependent signaling and kinase activity.
  • Examined nucleoporin phosphorylation and its interaction with Exportin-5 (XPO5).

Main Results:

  • Nuclear export of pre-miRNAs is accelerated subsequent to DNA damage.
  • This acceleration is dependent on ATM (Ataxia Telangiectasia Mutated) signaling.
  • ATM-activated AKT kinase phosphorylates Nup153, enhancing its interaction with XPO5.
  • Increased Nup153-XPO5 interaction leads to enhanced nuclear export of pre-miRNAs.

Conclusions:

  • DNA-damage signaling plays a critical role in regulating miRNA transport.
  • The ATM-AKT-Nup153-XPO5 axis is a key pathway for controlling pre-miRNA nuclear export after DNA damage.
  • This pathway is essential for miRNA maturation in response to DNA damage.

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