Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism

被引：98

作者：

Antoniali, Giulia ^{[1
]}

Serra, Fabrizio ^{[1
,8
]}

Lirussi, Lisa ^{[1
,9
,10
]}

Tanaka, Mikiei ^{[2
]}

D'Ambrosio, Chiara ^{[3
]}

Zhang, Shiheng ^{[4
]}

Radovic, Slobodanka ^{[5
]}

Dalla, Emiliano ^{[6
]}

Ciani, Yari ^{[6
]}

Scaloni, Andrea ^{[3
]}

Li, Mengxia ^{[4
]}

Piazza, Silvano ^{[6
,7
]}

Tell, Gianluca ^{[1
]}

机构：

[1] Univ Udine, Dept Med, Lab Mol Biol & DNA Repair, Ple M Kolbe 4, I-33100 Udine, Italy

[2] NHLBI, Biochem Lab, NIH, 50 South Dr,MSC 8012, Bethesda, MD 20892 USA

[3] Natl Res Council CNR Italy, Inst Anim Prod Syst Mediterranean Environm ISPAAM, Prote & Mass Spectrometry Lab, Via Argine 1085, I-80147 Naples, Italy

[4] Third Mil Med Univ, Canc Ctr Daping Hosp, Chongqing 400042, Peoples R China

[5] IGA Technol Serv Srl, Via J Linussio 51, I-33100 Udine, Italy

[6] Lab Nazl CIB, Area Sci Pk Padriciano, I-34149 Trieste, Italy

[7] Univ Trento, Bioinformat Core Facil, Ctr Integrat Biol, CIBIO, Via Sommarive 18, I-38123 Trento, TN, Italy

[8] IRCCS, Clin & Expt Onco Hematol Unit, Ctr Riferimento Oncol, Via Franco Gallini 2, I-33081 Aviano, PN, Italy

[9] Univ Oslo, Dept Clin Mol Biol, Sykehusveien 27, N-1474 Nordbyhagen, Norway

[10] Akershus Univ Hosp, Sykehusveien 27, N-1474 Nordbyhagen, Norway

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE-1; DIFFERENTIAL EXPRESSION ANALYSIS; CRITICAL LYSINE RESIDUES; GENOME-WIDE ANALYSIS; REPAIR ENZYME HAP1; N-TERMINAL DOMAIN; DNA-REPAIR; MESSENGER-RNA; TAMOXIFEN RESISTANCE; ALZHEIMERS-DISEASE;

D O I：

10.1038/s41467-017-00842-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mammalian apurinic/apyrimidinic endonuclease 1 is a DNA repair enzyme involved in genome stability and expression of genes involved in oxidative stress responses, tumor progression and chemoresistance. However, the molecular mechanisms underlying the role of apurinic/apyrimidinic endonuclease 1 in these processes are still unclear. Recent findings point to a novel role of apurinic/apyrimidinic endonuclease 1 in RNA metabolism. Through the characterization of the interactomes of apurinic/apyrimidinic endonuclease 1 with RNA and other proteins, we demonstrate here a role for apurinic/apyrimidinic endonuclease 1 in pri-miRNA processing and stability via association with the DROSHA-processing complex during genotoxic stress. We also show that endonuclease activity of apurinic/apyrimidinic endonuclease 1 is required for the processing of miR-221/222 in regulating expression of the tumor suppressor PTEN. Analysis of a cohort of different cancers supports the relevance of our findings for tumor biology. We also show that apurinic/apyrimidinic endonuclease 1 participates in RNA-interactomes and protein-interactomes involved in cancer development, thus indicating an unsuspected post-transcriptional effect on cancer genes.

引用

页数：18

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