Details

Autor(en) / Beteiligte

• Wan, Guohui
• Zhang, Xinna
• Langley, Robert R.
• Liu, Yunhua
• Hu, Xiaoxiao
• Han, Cecil
• Peng, Guang
• Ellis, Lee M.
• Jones, Stephen N.
• Lu, Xiongbin

Titel

DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT Pathway

Ist Teil von

• Cell reports (Cambridge), 2013-06, Vol.3 (6), p.2100-2112

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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. [Display omitted] •Pre-miRNA nuclear export is accelerated after DNA damage in an ATM-dependent manner•Interaction between Nup153 and XPO5 is enhanced after DNA damage•ATM-activated AKT kinase phosphorylates Nup153•Nup153 phosphorylation promotes nuclear export of pre-miRNAs Nuclear export of pre-microRNAs (pre-miRNAs) is a critical step in miRNA maturation. However, little is known about its regulation in the DNA-damage response. In this study, Lu and colleagues 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 and increased nuclear export of pre-miRNAs.