DNA damage modulates interactions between microRNAs and the 26S proteasome

// Anna S Tsimokha 1 , Valentina A. Kulichkova 1 , Elena V. Karpova 2 , Julia J. Zaykova 1 , Nikolai D Aksenov 1 , Anastasia A. Vasilishina 1 , Andrei V. Kropotov 1 , Alexey Antonov 3,4  and Nikolai A. Barlev 1,2,4 1 Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia 2 Department of Biochemistry, University of Leicester, Leicester, LE1 9HN 3 MRC Toxicology Unit, Leicester, LE1 9HN 4 Molecular Pharmacology laboratory, Saint-Petersburg Institute of Technology, Saint-Petersburg 190013, Russia Correspondence: Nikolai Barlev, email: // Keywords : 26S proteasome, miRNA, DNA damage, doxorubicin Received : April 4, 2014 Accepted : May 8, 2014 Published : May 9, 2014 Abstract 26S proteasomes are known as major non-lysosomal cellular machines for coordinated and specific destruction of ubiquitinylated proteins. The proteolytic activities of proteasomes are controlled by various post-translational modifications in response to environmental cues, including DNA damage. Besides proteolysis, proteasomes also associate with RNA hydrolysis and splicing. Here, we extend the functional diversity of proteasomes by showing that they also dynamically associate with microRNAs (miRNAs) both in the nucleus and cytoplasm of cells. Moreover, DNA damage induced by an anti-cancer drug, doxorubicin, alters the repertoire of proteasome-associated miRNAs, enriching the population of miRNAs that target cell cycle checkpoint regulators and DNA repair proteins. Collectively, these data uncover yet another potential mode of action for proteasomes in the cell via their dynamic association with microRNAs.