RNA Editing And ERV Effects During Early Embryonic Development In Mammals Based On Multi-omics

Stem cells with self-renewal ability and differentiation potential are key cells in the early embryonic development in mammals.The in-depth study of stem cells is the key to understanding the mechanisms of mammalian development and growth,is also a prerequisite for the application of stem cells in clinical regenerative medicine for the treatment of human diseases.In the m RNA level,RNA editing is a post-transcriptional modification that increases the diversity of eukaryotic transcriptomes and proteomes.Current research has found that RNA editing helps the production and maintenance of cancer stem cells.Mouse that have been knocked out of the ADAR enzyme may cause embryo death.At the DNA level,endogenous retroviruses are the remnants of past retroviral infections.Current research has found that these endogenous retroviruses are not dormant,they can provide promoters or enhancers for genes.Some HERVs have physiological effects,including affecting the formation of syncytiotrophoblast during placental development and intrinsic resistance to exogenous retroviral infections.However,there is currently a lack of studies on the dynamic changes of RNA editing and endogenous retroviruses throughout mammalian early embryonic development.And it is unclear whether there is a relationship between RNA editing and endogenous retroviruses.Therefore,obtaining the rules of early embryo development from the multi-omics level and searching for some genes related to cell stemness are important for studying embryonic stem cells and reprogramming.In this paper,we used multi-omics to analyze and compare the RNA-seq and ATAC-seq data of the human,mouse and pig during the early embryonic development.Mainly discussed the dynamic changes of the three RNA editing and endogenous retroviruses and the relationship between RNA editing and endogenous retroviruses.Although most RNA editing sites are located in the intergenic region,intron region and UTR region,there are also a few editing sites located in the CDS region,which play a non-synonymous role.Different endogenous retroviruses elements have stage-specific expression during early embryonic development and are related to embryonic development.RNA editing was also found in some endogenous retrovirus elements.Systematic RNA editing sites were identified in human,mouse and pig,and it was found that these three species had abundant editing sites during early embryonic development.With further attention to the coding region,4159,4516 and 16202 editing sites were identified in the protein coding regions of human,mouse and pig,respectively.Among them,after T test,it is found that the editing frequency of non-synonymous editing is lower than that of synonymous editing.We also found that the non-synonymous editing genes found in human and mouse are mainly related to embryonic development and cell division,while in pigs,these non-synonymous editing genes are mainly related to lipid metabolism.Therefore,we speculate that fat traits in pigs are regulated during early embryonic development.We did research on endogenous retroviruses during early embryonic development,the results show that the expression of different endogenous retroviruses is stage-specific during early embryonic development,with similar expression patterns to genes.At the same time,we used ATAC-seq data to detect all open regions of chromatin during early embryonic development and found that some open regions of chromatin cover certain the sequences of endogenous retroviruses.Further searching for motif on these sequences to identify related transcription factors,we found that there are endogenous retroviruses expressions upstream of stem-related genes,such as H1-8,POU5F1 and TCL1 A.We further explore the relationship between RNA editing and endogenous retroviruses.In this study,we analyzed the RNA editing on the endogenous retrovirus and found that there was also an RNA editing event on the endogenous retrovirus.Endogenous retroviruses can help to express some genes,and the expressed transcription factors are combined with the retroviral sequence,which in turn affects the expression of retroviruses or downstream genes.After RNA editing,transcription factors may no longer be able to bind to related motifs,thereby affecting the expression of stem-related genes,which in turn affects embryo development.In summary,we did a systematic analysis of RNA editing and endogenous retroviruses during early embryonic development.It was found that RNA editing is widespread in the early embryonic development of mammals.Many endogenous retroviruses in early embryonic development are located in the open chromatin region.RNA editing exists on endogenous retroviruses,which may affect downstream gene expression by affecting transcription factors.Based on the above conclusions,we have explored the molecular mechanisms affecting early embryonic development in many ways,providing ideas for studying reproductive development,solving genetic diseases,and regenerating stem cells.