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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Main Authors: Guohui Wan, Xinna Zhang, Robert R. Langley, Yunhua Liu, Xiaoxiao Hu, Cecil Han, Guang Peng, Lee M. Ellis, Stephen N. Jones, Xiongbin Lu
Format: Article
Language:English
Published: Elsevier 2013-06-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124713002714
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spelling 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.
url http://www.sciencedirect.com/science/article/pii/S2211124713002714
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