Identification and Bioinformatic Assessment of circRNA Expression After RMI1 Knockdown and Ionizing Radiation Exposure.

Abstract

RecQ-mediated genome instability protein 1 (RMI1) is an important component of the BLM-Topo IIIα-RMI1-RMI2 complex and plays a critical role in maintaining genome stability. However, the cellular functions of RMI1 in response to ionizing radiation (IR) are poorly understood. In this study, we found that RMI1 knockdown led to enhanced radiosensitivity and apoptosis after irradiation. To analyze the effect of RMI1 knockdown on the expression of circular RNAs (circRNAs), we performed high-throughput RNA sequencing on four groups of human embryonic kidney (HEK) 293T cells: control cells and RMI1 knockdown cells with or without IR exposure. A total of 179 and 160 differentially expressed circRNAs (DE-circRNAs) were identified under RMI1 knockdown without and with exposure to IR, respectively. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that these DE-circRNAs were involved in a variety of functions and signal pathways, including histone H3-K36 methylation, nuclear pore organization, mRNA destabilization, the mismatch repair pathway, and the apoptotic signaling pathway. Overall, our results indicate that RMI1 plays a crucial role in the response to IR and, more generally, that circRNAs are important in the regulatory mechanism of the radiation response.