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RNA Editing Regulates lnc RNA Splicing in Human Early Embryo Development

Jiajun Qiu, Xiao Ma, Fanyi Zeng, Jingbin Yan

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.

Introduction
Early 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.

Long non-coding RNAs (lncRNAs), which are typically >200 nucleotides in length, are involved in human early embryo development.

RNA editing is a molecular process perturbing RNA sequences in a co- or post-transcriptional manner. Thus far, >100 distinct types of RNA modifications have been identified.

Materials and methods

Single cell sequencing data

The dataset GSE44183 from NCBI contained 29 samples including 3 oocyte samples, 2 zygote samples, 3 2-cell stage samples, 4 4-cell stage samples, 11 8-cell stage samples, and 3 morula stage samples, which were consisted of pair-end sequencing data based on the Illumina HiSeq 2000 platform (Illumina, Inc.).

Discussion
Previous studies found there was a great change in gene expression profile during human embryo development. LncRNAs were found to play roles in mammal early embryo development, including human and mouse. LncRNAs have a stage-specific expression pattern during early embryo development, which is related to human oocyte maturation and human ZGA. Meanwhile, RNA editing was found to be able to affect the expression of lncRNAs. However, the detailed mechanism behind the regulation of RNA editing on lncRNAs remained unclear.

Citation: Qiu J, Ma X, Zeng F, Yan J (2021) RNA editing regulates lncRNA splicing in human early embryo development. PLoS Comput Biol 17(12): e1009630. https://doi.org/10.1371/journal.pcbi.1009630

Editor: Shi-Jie Chen, University of Missouri, UNITED STATES

Received: March 1, 2021; Accepted: November 11, 2021; Published: December 1, 2021.

Copyright: © 2021 Qiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The dataset GSE44183 was used for this manuscript from NCBI database, which is allowed for further use. The pipeline we used is uploaded to github:https://github.com/JiajunQiu/RNAediting_Pipeline.

Funding: Fanyi Zeng is supported by the grants from the National Key Research and Development Program of China (2019YFA0801402) and Shanghai key clinical specialty project (shslczdzk05705). Jingbin Yan is supported by the grant from the National Natural Science Foundation of China (81971421). Jiajun Qiu is sponsored by Shanghai Sailing Program (21YF1424200) and the China Scholarship Council (CSC201606230244). Xiao Ma is supported by the China Scholarship Council (CSC201708080070). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

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