The Circular RNome of Developmental Retina in Mice
The Circular RNome of Developmental Retina in Mice
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小鼠发育视网膜的圆形RNome
DOI：
10.1016/j.omtn.2019.11.016
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发表时间：
2020-03-06
影响因子：
8.8
通讯作者：
Jin, Zi-Bing
中科院分区：
文献类型：
--
作者：
Chen, Xue-Jiao;Zhang, Zi-Cheng;Jin, Zi-Bing
环状RNA（CircRNA）是一类表达模式广泛的非编码RNA，是基因组调控网络的重要组成部分。迄今为止，视网膜（中枢神经系统的关键部分）中circRNA的表达模式和调节效力尚未得到很好的理解。在这项研究中，来自小鼠视网膜发育的五个阶段（E18.5，P1，P7，P14和P30）的RNA被测序。总共鉴定了9，029个circRNA。大多数circRNA在不同的阶段表达，具有特定的签名，并且它们的表达模式不同于它们的宿主线性转录物。一些circRNA可以充当几种视网膜microRNA（miRNAs）的海绵。此外，circTulp4可以作为竞争性内源性RNA（ceRNA）来调节靶基因。值得注意的是，在体内沉默circTulp4导致小鼠具有薄的外核层（ONL）和缺陷的视网膜功能。此外，我们发现，在视网膜变性模型（rd8小鼠）中，circRNA在比疾病发作早得多的时间点失调。总之，我们提供了视网膜发育过程中的第一个circRNA表达图谱，并强调了circRNA在视网膜发育和变性中的关键生物学作用。
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.