Exposure to Ionizing Radiation Triggers Prolonged Changes in Circular RNA Abundance in the Embryonic Mouse Brain and Primary Neurons

Abstract

The exposure of mouse embryos in utero and primary cortical neurons to ionizing radiation results in the P53-dependent activation of a subset of genes that is highly induced during brain development and neuronal maturation, a feature that these genes reportedly share with circular RNAs (circRNAs). Interestingly, some of these genes are predicted to express circular transcripts. In this study, we validated the abundance of the circular transcript variants of four P53 target genes (Pvt1, Ano3, Sec14l5, and Rnf169). These circular variants were overall more stable than their linear counterparts. They were furthermore highly enriched in the brain and their transcript levels continuously increase during subsequent developmental stages (from embryonic day 12 until adulthood), while no further increase could be observed for linear mRNAs beyond post-natal day 30. Finally, whereas radiation-induced expression of P53 target mRNAs peaks early after exposure, several of the circRNAs showed prolonged induction in irradiated embryonic mouse brain, primary mouse cortical neurons, and mouse blood. Together, our results indicate that the circRNAs from these P53 target genes are induced in response to radiation and they corroborate the findings that circRNAs may represent biomarkers of brain age. We also propose that they may be superior to mRNA as long-term biomarkers for radiation exposure.

Knockdown of PVT1 Exerts Neuroprotective Effects against Ischemic Stroke Injury through Regulation of miR-214/Gpx1 Axis

“…PVT1 was reported to be involved in several central neuronal system diseases [ 29 , 30 ]. For instance, silence of PVT1 decreased the loss of neurons and inhibited the activation of astrocytes in hippocampus tissues of epileptic rats [ 31 ].…”

Analysis of circRNA-miRNA-mRNA Regulatory Network in Peripheral Blood of Radiation Workers

“…Researchers found that circRNA was associated with many biomarkers of ionizing radiation injury, such as mouse brain and primary neuron injury, mouse bone marrow injury, and radiation-related esophageal injury. 20 , 21 , 11 In addition, it is also found that circRNA is related to a variety of radiation diseases, such as hsa_circ_0001649 participating in the following regulation of migration and proliferation of cholangiocarcinoma cells after radiotherapy, and hsa_circRNA_ 100367 regulating radiosensitivity of esophageal cancer through Wnt pathway. 22 , 23 The miRNA is an evolutionary conservative small molecule with a length of 18–25 nucleotides.…”

Circular RNAs: Novel potential regulators in embryogenesis, female infertility, and pregnancy‐related diseases

“…Exposure to environmental pollution factors has been associated with defects during embryonic development as well as postpartum complications such as neonatal malformation and birth defects. Mfossa et al (2019) reported that exposure to ionizing radiation activated transcriptome of P53‐target genes to induce circular transcripts in mouse embryos and primary neurons. In response to radiation, expression of linear transcripts of P53 target genes peaked earlier than circRNAs in embryonic brain and primary cortical neurons.…”