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

Giulia Antoniali, Fabrizio Serra, Lisa Lirussi, Mikiei Tanaka, Chiara D’Ambrosio, Shiheng Zhang, Slobodanka Radovic, Emiliano Dalla, Yari Ciani, Andrea Scaloni, Mengxia Li (), Silvano Piazza () and Gianluca Tell ()
Additional contact information
Giulia Antoniali: University of Udine
Fabrizio Serra: University of Udine
Lisa Lirussi: University of Udine
Mikiei Tanaka: National Institutes of Health
Chiara D’Ambrosio: Institute for the Animal Production System in the Mediterranean Environment (ISPAAM) National Research Council (CNR) of Italy
Shiheng Zhang: Third Military Medical University
Slobodanka Radovic: IGA Technology Services srl
Emiliano Dalla: Area Science Park Padriciano
Yari Ciani: Area Science Park Padriciano
Andrea Scaloni: Institute for the Animal Production System in the Mediterranean Environment (ISPAAM) National Research Council (CNR) of Italy
Mengxia Li: Third Military Medical University
Silvano Piazza: Area Science Park Padriciano
Gianluca Tell: University of Udine

Nature Communications, 2017, vol. 8, issue 1, 1-18

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00842-8

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