RNA editing regulates lncRNA splicing in human early embryo development

Area of Science:

• Molecular Biology
• Developmental Biology
• Genetics

Background:

• RNA editing is a co- or post-transcriptional modification altering RNA sequences.
• Previous research linked RNA editing to cancer and aging.
• The role of RNA editing in early human embryonic development remains largely unknown.

Purpose of the Study:

• To investigate the function and patterns of RNA editing during human early embryo development.
• To explore the relationship between RNA editing and long non-coding RNA (lncRNA) splicing.
• To identify potential roles of RNA editing in developmental processes and birth defects.

Main Methods:

• Analysis of single-cell RNA sequencing data from human early embryos.
• Statistical analysis of differential RNA editing ratios across developmental stages.
• Correlation analysis between RNA editing rates and splicing indices (PSI) of lncRNA exons.
• Functional enrichment analysis of RNA editing-regulated lncRNAs.

Main Results:

• 36.7% of RNA editing sites showed differential editing ratios during early development.
• A significant reprogramming of RNA editing rates was observed at the 8-cell stage, with 99.2% of sites showing decreased editing.
• RNA editing preferentially occurred on splicing sites, particularly for lncRNAs (OR=2.19), compared to mRNAs (OR=0.22).
• RNA editing rates on lncRNAs strongly correlated with lncRNA exon splicing (R=0.75).
• RNA editing-regulated lncRNAs were enriched in pathways like signal transduction and mitochondrial calcium ion transport.

Conclusions:

• RNA editing plays a dynamic role in human early embryonic development, with notable changes at the 8-cell stage.
• RNA editing, especially in lncRNAs, appears to regulate RNA splicing during development.
• These findings offer new insights into RNA editing mechanisms in lncRNAs, impacting developmental biology and potentially common birth defects.