DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT Pathway
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...
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2013-06-01
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doaj-9cbd6a84242d4851b37977e2eb99e6532020-11-25T01:09:26ZengElsevierCell Reports2211-12472013-06-01362100211210.1016/j.celrep.2013.05.038DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT PathwayGuohui Wan0Xinna Zhang1Robert R. Langley2Yunhua Liu3Xiaoxiao Hu4Cecil Han5Guang Peng6Lee M. Ellis7Stephen N. Jones8Xiongbin Lu9Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USADepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 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. http://www.sciencedirect.com/science/article/pii/S2211124713002714 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guohui Wan Xinna Zhang Robert R. Langley Yunhua Liu Xiaoxiao Hu Cecil Han Guang Peng Lee M. Ellis Stephen N. Jones Xiongbin Lu |
spellingShingle |
Guohui Wan Xinna Zhang Robert R. Langley Yunhua Liu Xiaoxiao Hu Cecil Han Guang Peng Lee M. Ellis Stephen N. Jones Xiongbin Lu DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT Pathway Cell Reports |
author_facet |
Guohui Wan Xinna Zhang Robert R. Langley Yunhua Liu Xiaoxiao Hu Cecil Han Guang Peng Lee M. Ellis Stephen N. Jones Xiongbin Lu |
author_sort |
Guohui Wan |
title |
DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT Pathway |
title_short |
DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT Pathway |
title_full |
DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT Pathway |
title_fullStr |
DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT Pathway |
title_full_unstemmed |
DNA-Damage-Induced Nuclear Export of Precursor MicroRNAs Is Regulated by the ATM-AKT Pathway |
title_sort |
dna-damage-induced nuclear export of precursor micrornas is regulated by the atm-akt pathway |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-06-01 |
description |
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.
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url |
http://www.sciencedirect.com/science/article/pii/S2211124713002714 |
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