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

Cell Rep. 2013 Jun 27;3(6):2100-12. doi: 10.1016/j.celrep.2013.05.038. Epub 2013 Jun 20.


Expression of microRNAs (miRNAs) involves transcription of miRNA genes and maturation of the primary transcripts. Recent studies have shown that posttranscriptional processing of primary and precursor miRNAs is induced after DNA damage through regulatory RNA-binding proteins in the Drosha and Dicer complexes, such as DDX5 and KSRP. However, little is known about the regulation of nuclear export of pre-miRNAs in the DNA-damage response, a critical step in miRNA maturation. Here, we show that nuclear export of pre-miRNAs is accelerated after DNA damage in an ATM-dependent manner. The ATM-activated AKT kinase phosphorylates Nup153, a key component of the nucleopore, leading to enhanced interaction between Nup153 and Exportin-5 (XPO5) and increased nuclear export of pre-miRNAs. These findings define an important role of DNA-damage signaling in miRNA transport and maturation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Animals
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • DNA Damage*
  • HCT116 Cells
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction


  • Karyopherins
  • MicroRNAs
  • NUP153 protein, human
  • Nuclear Pore Complex Proteins
  • XPO5 protein, human
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Proto-Oncogene Proteins c-akt

Associated data

  • GEO/GSE42248