DNA damage-induced upregulation of miR-709 in the germline downregulates BORIS to counteract aberrant DNA hypomethylation

Abstract

MicroRNAs as potent regulators of gene expression are involved in spermatogenesis, yet their role in response of germline to genotoxic stress is obscure. We studied the microRNAome profile of X-ray irradiated mouse testes using the microarray technique. We found that radiation exposure significantly affected microRNA expression in testes. Mir-709 was the most abundant in both control and irradiated testes, and a big difference in miR-709 levels was observed between the control and exposed group. We found that miR-709 targets the Brother of the Regulator of Imprinted Sites (BORIS), an important regulator of DNA methylation and imprinting. Here, we for the first time show that the DNA damage-induced and ATR/Rfx1-mediated increase of miR-709 expression in exposed testes may be a protective mechanism that effectively decreases a cellular level of BORIS to prevent massive aberrant erasure of DNA methylation after radiation exposure.