Micro(mi) RNA-34a targets protein phosphatase (PP)1γ to regulate DNA damage tolerance.

ABSTRACT: The DNA damage response (DDR) triggers widespread changes in gene expression, mediated partly by alterations in micro(mi) RNA levels, whose nature and significance remain uncertain. Here, we report that miR-34a, which is upregulated during the DDR, modulates the expression of protein phosphatase 1γ (PP1γ) to regulate cellular tolerance to DNA damage. Multiple bio-informatic algorithms predict that miR-34a targets the PP1CCC gene encoding PP1γ protein. Ionising radiation (IR) decreases cellular expression of PP1γ in a dose-dependent manner. An miR-34a-mimic reduces cellular PP1γ protein. Conversely, an miR-34a inhibitor antagonizes IR-induced decreases in PP1γ protein expression. A wild-type (but not mutant) miR-34a seed match sequence from the 3' untranslated region (UTR) of PP1CCC when tr

SUBMITTER: Takeda Y 

PROVIDER: S-EPMC4825746 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature