The ATM Kinase Induces MicroRNA Biogenesis in the DNA Damage Response

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2011 Feb 19

PMID 21329876

Citations 124

Authors

Xinna Zhang

Guohui Wan

Franklin G Berger

Xiaoming He

Xiongbin Lu

Affiliations

Soon will be listed here.

Abstract

The DNA damage response involves a complex network of processes that detect and repair DNA damage. Here we show that miRNA biogenesis is globally induced upon DNA damage in an ATM-dependent manner. About one-fourth of miRNAs are significantly upregulated after DNA damage, while loss of ATM abolishes their induction. KH-type splicing regulatory protein (KSRP) is a key player that translates DNA damage signaling to miRNA biogenesis. The ATM kinase directly binds to and phosphorylates KSRP, leading to enhanced interaction between KSRP and pri-miRNAs and increased KSRP activity in miRNA processing. Mutations of the ATM phosphorylation sites of KSRP impaired its activity in regulating miRNAs. These findings reveal a mechanism by which DNA damage signaling is linked to miRNA biogenesis.

Citing Articles

Emerging roles of bases modifications and DNA repair proteins in onco-miRNA processing: novel insights in cancer biology.

Mangiapane G, DAgostino V, Tell G Cancer Gene Ther. 2024; 31(12):1765-1772.

PMID: 39322751 DOI: 10.1038/s41417-024-00836-x.

Radio-miRs: a comprehensive view of radioresistance-related microRNAs.

Pedroza-Torres A, Romero-Cordoba S, Montano S, Peralta-Zaragoza O, Velez-Uriza D, Arriaga-Canon C Genetics. 2024; 227(4).

PMID: 38963803 PMC: 11304977. DOI: 10.1093/genetics/iyae097.

Elucidation of how the Mir-23-27-24 cluster regulates development and aging.

Yap X, Chen J Exp Mol Med. 2024; 56(6):1263-1271.

PMID: 38871817 PMC: 11263685. DOI: 10.1038/s12276-024-01266-3.

Drug resistance in ovarian cancer: from mechanism to clinical trial.

Wang L, Wang X, Zhu X, Zhong L, Jiang Q, Wang Y Mol Cancer. 2024; 23(1):66.

PMID: 38539161 PMC: 10976737. DOI: 10.1186/s12943-024-01967-3.

Acetylated KHSRP impairs DNA-damage-response-related mRNA decay and facilitates prostate cancer tumorigenesis.

Yuan H, Cai R, Chen B, Wang Q, Wang M, An J Mol Oncol. 2024; 18(9):2314-2330.

PMID: 38501452 PMC: 11467790. DOI: 10.1002/1878-0261.13634.

References

Maya R, Balass M, Kim S, Shkedy D, Leal J, Shifman O . ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev. 2001; 15(9):1067-77. PMC: 312683. DOI: 10.1101/gad.886901. View

Briata P, Forcales S, Ponassi M, Corte G, Chen C, Karin M . p38-dependent phosphorylation of the mRNA decay-promoting factor KSRP controls the stability of select myogenic transcripts. Mol Cell. 2005; 20(6):891-903. DOI: 10.1016/j.molcel.2005.10.021. View

Suzuki H, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K . Modulation of microRNA processing by p53. Nature. 2009; 460(7254):529-33. DOI: 10.1038/nature08199. View

Kim S, Lim D, Canman C, Kastan M . Substrate specificities and identification of putative substrates of ATM kinase family members. J Biol Chem. 1999; 274(53):37538-43. DOI: 10.1074/jbc.274.53.37538. View

Merritt W, Lin Y, Han L, Kamat A, Spannuth W, Schmandt R . Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 2008; 359(25):2641-50. PMC: 2710981. DOI: 10.1056/NEJMoa0803785. View

Banin S, Moyal L, Shieh S, Taya Y, Anderson C, Chessa L . Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science. 1998; 281(5383):1674-7. DOI: 10.1126/science.281.5383.1674. View

Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K . DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 2005; 434(7035):864-70. DOI: 10.1038/nature03482. View

Hu H, Du L, Nagabayashi G, Seeger R, Gatti R . ATM is down-regulated by N-Myc-regulated microRNA-421. Proc Natl Acad Sci U S A. 2010; 107(4):1506-11. PMC: 2824372. DOI: 10.1073/pnas.0907763107. View

Trabucchi M, Briata P, Garcia-Mayoral M, Haase A, Filipowicz W, Ramos A . The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature. 2009; 459(7249):1010-4. PMC: 2768332. DOI: 10.1038/nature08025. View

10.

Ziv Y, Bielopolski D, Galanty Y, Lukas C, Taya Y, Schultz D . Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat Cell Biol. 2006; 8(8):870-6. DOI: 10.1038/ncb1446. View

11.

Lee Y, Kim M, Han J, Yeom K, Lee S, Baek S . MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004; 23(20):4051-60. PMC: 524334. DOI: 10.1038/sj.emboj.7600385. View

12.

Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L . The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008; 14(11):1271-7. DOI: 10.1038/nm.1880. View

13.

Davis B, Hata A . Regulation of MicroRNA Biogenesis: A miRiad of mechanisms. Cell Commun Signal. 2009; 7:18. PMC: 3224893. DOI: 10.1186/1478-811X-7-18. View

14.

Ruggiero T, Trabucchi M, Ponassi M, Corte G, Chen C, Al-Haj L . Identification of a set of KSRP target transcripts upregulated by PI3K-AKT signaling. BMC Mol Biol. 2007; 8:28. PMC: 1858702. DOI: 10.1186/1471-2199-8-28. View

15.

Cimmino A, Calin G, Fabbri M, Iorio M, Ferracin M, Shimizu M . miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005; 102(39):13944-9. PMC: 1236577. DOI: 10.1073/pnas.0506654102. View

16.

Gherzi R, Trabucchi M, Ponassi M, Ruggiero T, Corte G, Moroni C . The RNA-binding protein KSRP promotes decay of beta-catenin mRNA and is inactivated by PI3K-AKT signaling. PLoS Biol. 2006; 5(1):e5. PMC: 1702562. DOI: 10.1371/journal.pbio.0050005. View

17.

Garcia-Mayoral M, Hollingworth D, Masino L, Diaz-Moreno I, Kelly G, Gherzi R . The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation. Structure. 2007; 15(4):485-98. DOI: 10.1016/j.str.2007.03.006. View

18.

Matsuoka S, Ballif B, Smogorzewska A, McDonald 3rd E, Hurov K, Luo J . ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007; 316(5828):1160-6. DOI: 10.1126/science.1140321. View

19.

Zhang X, Wan G, Mlotshwa S, Vance V, Berger F, Chen H . Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway. Cancer Res. 2010; 70(18):7176-86. PMC: 2940956. DOI: 10.1158/0008-5472.CAN-10-0697. View

20.

Durocher D, Jackson S . DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme?. Curr Opin Cell Biol. 2001; 13(2):225-31. DOI: 10.1016/s0955-0674(00)00201-5. View