LncRNA Inc-RIregulates homologous recombination repair of DNA double-strand breaks by stabilizing RAD51mRNA as a competitive endogenous RNA

Abstract

DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. The current models of the mechanism of DSB repair are based on studies of DNA repair proteins. Long non-coding RNAs (IncRNAs) have recently emerged as new regulatory molecules, with diverse functions in biological processes. In the present study, we found that expression of the ionizing radiation-inducible IncRNA, Inc-RI, was correlate negatively with micronucleus frequencies in human peripheral blood lymphocytes. Knockdown of Inc-RIsignificantly increased spontaneous DSBs levels, which was confirmed to be associated with the decreased efficiency of homologous recombination (HR) repair of DSBs. The expression of RAD51, a key recombinase in the HR pathway, decreased sharply in Inc-RI-depressed cells. In a further investigation, we demonstrated that miR-193a-3p could bind with both Inc-RI and RAD51 mRNA and depressed the expression of Inc-RIand RAD51 mRNA. Lnc-RI acted as a competitive endogenous RNA (ceRNA) to stabilize RAD51mRNA via competitive binding with miR-193a-3p and release of its inhibition of RAD51expression. To our knowledge, this is the first study to demonstrate the role of Inc-RI in regulating HR repair of DSBs. The feedback loop established in the current study suggests that Inc-RI is critical for the maintenance of genomic stability.