title: miR-3928 activates ATR pathway by targeting Dicer.
abstract: 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.
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chang
authors.forename: Wentao
authors.initials: W
authors.lastname: Hu
authors.forename: Caiyong
authors.initials: C
authors.lastname: Ye
authors.forename: Bin
authors.initials: B
authors.lastname: Yao
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.forename: Nan
authors.initials: N
authors.lastname: Ding
authors.forename: Jufang
authors.initials: J
authors.lastname: Wang
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D064007:Ataxia Telangiectasia Mutated Proteins; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D014965:X-Rays
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; D035683:MicroRNAs; D011494:Protein Kinases; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases