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

Author

Listed:
  • Giulia Antoniali

    (University of Udine)

  • Fabrizio Serra

    (University of Udine
    Centro di Riferimento Oncologico, I.R.C.C.S.)

  • Lisa Lirussi

    (University of Udine
    University of Oslo and Akershus University Hospital)

  • 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
    University of Trento)

  • Gianluca Tell

    (University of Udine)

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.

Suggested Citation

  • 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 &, 2017. "Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00842-8
    DOI: 10.1038/s41467-017-00842-8
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