Genome-wide characterization of RNA editing highlights roles of high editing events of glutamatergic synapse during mouse retinal development

Computational and Structural Biotechnology Journal

Xinrui Shi¹  Jianzhong Su²  Lijun Dai²  Meng Zhou²  Jiaying Yang²  Chenghao Li²  Yan Zhang²  Ke Li² 

[1] Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China;School of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China;

关键词: RNA editing;    Retinal development;    Non-synonymous;    Bipolar cells;    Retinal ganglion cells;   

DOI  :  

来源: DOAJ

【 摘 要 】

Adenosine-to-inosine (A-to-I) RNA editing leads to functional change of neurotransmitter receptor which is essential for neurotransmission and normal neuronal development. As a highly accessible part of central nervous system, retina has been extensively studied, however, it remains largely unknown how RNA editing regulates its development. Here, a genome-wide screening of high-confidence RNA editing events were performed to decipher the dynamic transcriptome regulation by RNA editing during mouse retinal development. 2000 high-confidence editing sites across eight developmental stages of retina were called. Three unique patterns (RNA-editinghigh pattern, RNA-editingmedium pattern and RNA-editinglow pattern) were identified by clustering these editing sites based on their editing level during retinal development. Editing events from RNA-editinghigh pattern were significantly associated with glutamate receptors and regulated synaptic transmission. Interestingly, most non-synonymous high-editing sites were mapped to ion channel genes of glutamatergic synapse which were associated with neurotransmission by controlling ion channel permeability and affecting exocytosis. Meanwhile, these non-synonymous editing sites were evolutionarily conserved and exhibited a consistently increasing editing levels between mouse and human retinal development. Single-cell RNA-seq data analysis revealed that RNA editing events prefer to occur in two main cell types including bipolar and amacrine cells. Genes with non-synonymous high-editing sites were enriched in both bipolar cells and retina ganglion cells, which may mediate retina ganglion cell differentiation by altering channel ion permeability. Together, our results provide novel insights into mechanism of post-transcriptional regulation during retinal development and help to develop novel RNA editing-guided therapeutic strategies for retinal disorders.

【 授权许可】

Unknown