title: DNA damage modulates interactions between microRNAs and the 26S proteasome.
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.
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Tsimokha
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Kulichkova
authors.forename: Elena V
authors.initials: EV
authors.lastname: Karpova
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Zaykova
authors.forename: Nikolai D
authors.initials: ND
authors.lastname: Aksenov
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Vasilishina
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Kropotov
authors.forename: Alexey
authors.initials: A
authors.lastname: Antonov
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia; Department of Biochemistry, University of Leicester, Leicester, LE1 9HN; Molecular Pharmacology laboratory, Saint-Petersburg Institute of Technology, Saint-Petersburg 190013, Russia.
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Barlev
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D020014:K562 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D035683:MicroRNAs; D004317:Doxorubicin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease