Multi-tissue transition of A-to-I RNA editing pattern and its regulatory relevance in transcription, splicing, and translation during development

Abstract

AbstractPrevious studies have shown that A-to-I RNA editing can occur in various organs and tissues of normal physiological conditions. However, the dynamics of RNA editing and its functional relevance in multiple tissues and organs during the embryo-to-adult transition in mammals remains to be elucidated. Herein, we performed a comprehensive analysis of RNA sequencing and ribosome profiling of six mouse tissues at embryonic and adult stages, to elucidate the tissue- and stage-specific landscape of A-to-I RNA editing. Our result identified transcriptome-wide A-to-I RNA editing in six tissue types. Furthermore, differential expression was concurrently observed in a set of distinct differential RNA editing genes at both mRNA and protein levels across different tissues. Gene function and pathway enrichment analysis indicated that these genes with both differential editing and expression were involved in not only tissue-specific biological functions, but also common fundamental processes of post-transcriptional and post-translational modification. Further analysis showed a dynamic interaction between A-to-I RNA editing and alternative splicing in cell survival, death, signal transduction, and cell-cell interactions during development. Overall, our study demonstrates the potential role played by A-to-I editing during development, providing new insight into the effects of RNA editing within both transcriptional and translational landscape on it.