Functions Of MiR-1011 And MiR-318 At DNA Damage Response

The stability of the genome is continuously challenged by DNA lesions,DNA damage events each cell by hundreds of thousands of times a day.These DNA damage caused by normal cell metabolism waste or DNA replication stress,can also be caused by radiation and chemicals in environment.DNA damage in lymphocytes and reproductive cells,can also be caused by genome rearrangement.DNA damage can intervene in DNA replication and transcription,and leads to gene mutation and chromosome break disorders.Maintains the stability of the genome DNA damage response system,eliminate the negative result of DNA damage,daughter cells to stop them.DNA damage response system defects will lead to aging and various disorders including developmental defect,degenerative neurological disease and cancer.Therefore,an efficient DNA damage response system is important to the survival of the cells and organisms.MiRNA is a size about 18~22bp noncoding RNA molecules.miRNA adjust the target gene transcription level through a combination of target gene mRNA 3 'UTR region of miRNA and miRNA adjust target gene transcription by homology mRNA specific inhibition of specific cutting or protein synthesis.Recent studies have identified miRNAs maturity required for a variety of subunit protein complexes and named it the microprocessor.Microprocessor includes: Drosha,RNase III endonuclease and DGCR8.Predicted in roughly 2000 human miRNAs,more than 900 miRNAs have been confirmed,adjust the 30% of human genes.miRNA in addition to the normal development and cell physiological process plays an important function,as the study found that the miRNA function disorder is helpful to human disease,the disorder can result in neurodegenerative diseases,tumor,cardiovascular disease and some other diseases.This DNA-damage response encompasses gene-expression regulation at the transcriptional and posttranslational levels.miRNA as a noncoding RNA,miRNA transcription and post-transcription level is adjusted after DNA damage.Objective A lot of researches demonstrated functions of miRNA at DNA damage response in vitro.However,in Drosophila functions of miRNA at DNA damage response are a lack of systematic research.here,we used Drosophila mutants to explore the fuctions of p53-dependent and-independent miRNA in DNA damage.Method 1:The laboratory previous screened 46 p53-dependent and-independent differential expression miRNAs through RNA-seq.2:Through molecular cloning,The research constructs miRNAs g RNA and miRNAs transgene plasmids.3:Through irradiation method,The research study whether mir-1011?mir-318?mir-278? mir-8 ?mir-932 ?mir-375?mir-9c?mir-274 mutants Drosophila hypersensitive to irradiation.4:Through Brd U staining,The research study whether mir-1011?mir-318 affect G1/S checkpoint.5:Through PH3 staining,The research study whether mir-1011?mir-318 affect G2/M checkpoint.Result 1:The study constructs 21 miRNAs g RNA and 22 miRNAs transgene plasmids.2:The study found mir-1011 ?mir-318 and mir-278 mutants Drosophila were hypersensitive to irradiation;mir-8 mutants Drosophila was slightly hypersensitive to irradiation;mir-932 mutants Drosophila was irradiation resistance;mir-375?mir-9c?mir-274 mutants Drosophila weren't hypersensitive to irradiation.3:The study found mir-1011 participated DNA damage response through regulating G1/S checkpoint.4:The study found mir-318 didn't affect G1/S and G2/M checkpoint.