Abstract
RNA editing is a co- or post-transcriptional modification through which some cells can make discrete changes to specific nucleotide sequences within an RNA molecule after transcription. Previous studies found that RNA editing may be critically involved in cancer and aging. However, the function of RNA editing in human early embryo development is still unclear. In this study, through analyzing single cell RNA sequencing data, 36.7% RNA editing sites were found to have a have differential editing ratio among early embryo developmental stages, and there was a great reprogramming of RNA editing rates at the 8-cell stage, at which most of the differentially edited RNA editing sites (99.2%) had a decreased RNA editing rate. In addition, RNA editing was more likely to occur on RNA splicing sites during human early embryo development. Furthermore, long non-coding RNA (lncRNA) editing sites were found more likely to be on RNA splicing sites (odds ratio = 2.19, P = 1.37×10−8), while mRNA editing sites were less likely (odds ratio = 0.22, P = 8.38×10−46). Besides, we found that the RNA editing rate on lncRNA had a significantly higher correlation coefficient with the percentage spliced index (PSI) of lncRNA exons (R = 0.75, P = 4.90×10−16), which indicated that RNA editing may regulate lncRNA splicing during human early embryo development. Finally, functional analysis revealed that those RNA editing-regulated lncRNAs were enriched in signal transduction, the regulation of transcript expression, and the transmembrane transport of mitochondrial calcium ion. Overall, our study might provide a new insight into the mechanism of RNA editing on lncRNAs in human developmental biology and common birth defects.
Highlights
Embryo development is a complicated biological process in which a large number of genes and factors are involved
Through analyzing the sequencing data and computational biology, we found that RNA editing could regulate the alternative splicing of long-noncoding RNAs in human early embryo development
The reason could be DEseq and DEsingle are better at the raw read count data, while MAST is more suitable for transcripts per million (TPM) data
Summary
Embryo development is a complicated biological process in which a large number of genes and factors are involved. Dynamic changes in gene expression were found during human early embryo development [1]. Each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. The sequential order of transcriptional changes in pathways of the cell cycle, gene regulation, translation, and metabolism, act in a step-wise manner from cleavage to morula [2]. The molecular mechanism behind the dynamic changes in gene expression during early embryo development is still unclear. Zygotic genome activation (ZGA) at 8-cell stage promotes a remarkable reprogramming of gene expression patterns, coupled with the generation of novel transcripts that are not expressed in oocytes. The mechanism by which ZGA achieves such reprogramming needs to be further studied [3]
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