Placental Editome Profiling Reveals Widespread RNA-Editing Dysregulation in Preeclampsia

Dysregulated RNA editing is well documented in several diseases such as cancer. The extent to which RNA editing might be involved in diseases originated in the placenta such as preeclampsia remains unknown, because RNA editing has rarely been studied in the placenta. Here, the RNA editome is systematically profiled on placentae from 9 patients with early-onset severe preeclampsia (EOSPE) and 32 normal controls, and a widespread RNA editing dysregulation in EOSPE has been identified. The mis-edited gene set is enriched with known preeclampsia-associated genes and differentially expressed genes in EOSPE. The “RNA editing events” at two microRNA binding sites in 3’-UTR of the LEP mRNA have been generated, which leads to increased expression level of LEP in trophoblast cells. Upregulation of LEP is also observed in the placentae of PE patients. These results suggest that widespread placental RNA editing may be involved in placental development and dysregulation of RNA editing in the placenta may contribute to the pathogenesis of preeclampsia. Placentae from 9 patients with early-onset severe preeclampsia (EOSPE) and 32 normal controls were used for RNA-sequencing on the Hiseq2500 platform. Sequences were aligned to human transcriptome (hg38). RNA editing sites were detected by GATK and annotated by ANNOVAR. RNA editing levels were calculated from RNA-sequencing reads. Editing levels between EOSPE and normal groups were compared to detect dysregulated RNA editing events. Gene expressions were estimated by htseq-count and differentially expressed genes were detected by comparing expression levels between two groups. Correlation between RNA editing levels and gene expressions were calculated to detect RNA editing events that might associate with expression regulating.