miR-3928 activates ATR pathway by targeting Dicer

• DOI: 10.4161/rna.21821
• Publication Date: 2012-10-09T14:04:29Z
• Authors: Lei Chang; Wentao Hu; Caiyong Ye; Bin Yao; Lei Song; Xin Wu; Nan Ding; Jufang Wang; Guangming Zhou
• Keywords: Ribonuclease III; 0303 health sciences; Binding Sites; X-Rays; Cell Cycle Proteins; Ataxia Telangiectasia Mutated Proteins; Protein Serine-Threonine Kinases; G1 Phase Cell Cycle Checkpoints; DEAD-box RNA Helicases; MicroRNAs; 03 medical and health sciences; Gene Expression Regulation; Cell Line, Tumor; Checkpoint Kinase 1; Humans; 3' Untranslated Regions; Protein Kinases; Signal Transduction

Alterations in microRNA (miRNA) expression have been observed in cells subjected to exogenous stresses, implying that miRNAs play an important role in cellular stress response; however, the underlying mechanism is still largely unknown. In the present study, we found that miR-3928 was implicated in cellular response to ionizing radiation. After exposed to X-rays, miR-3928 expression increased in 1.5 h and then decreased, meanwhile Dicer, a key component in the miRNA processing machinery, increased gradually. An oscillation was observed in the expression of both mature miR-3928 and Dicer mRNA from 2 h to 3.5 h in irradiated cells. Then, we verified that miR-3928 directly bound to the 3'-untranslated region of Dicer mRNA. Consequently, Dicer expression was suppressed and the maturation of other miRNAs including miR-185, miR-300, and miR-663, was inhibited. Overexpression of miR-3928 induced DNA damage, activated ATR, and phosphorylated Chk1 accompanied by G1 arrest. Taken together, these findings replenished ATR/Chk1 pathway by revealing a novel miRNA regulatory network in response to exogenous stress, in which miR-3928 plays an important role in regulating the expression of Dicer.