The Circular RNome of Developmental Retina in Mice

Circular RNAs (circRNAs) represent a class of noncoding RNAs with a wide expression pattern, and they constitute an important layer of the genome regulatory network. To date, the expression pattern and regulatory potency of circRNAs in the retina, a key part of the central nervous system, are not yet well understood. In this study, RNAs from five stages (E18.5, P1, P7, P14, and P30) of mouse retinal development were sequenced. A total of 9,029 circRNAs were identified. Most circRNAs were expressed in different stages with a specific signature, and their expression patterns were different from those of their host linear transcripts. Some circRNAs could act as sponges for several retinal microRNAs (miRNAs). Furthermore, circTulp4 could function as a competitive endogenous RNA (ceRNA) to regulate target genes. Remarkably, silencing circTulp4 in vivo led to mice having a thin outer nuclear layer (ONL) and defective retinal function. In addition, we found that circRNAs were dysregulated at a much earlier time point than that of disease onset in a retinal degeneration model (rd8 mice). In summary, we provide the first circRNA expression atlas during retinal development and highlight a key biological role for circRNAs in retinal development and degeneration.