Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed
Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed
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DOI：
10.1016/j.molcel.2015.03.027
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发表时间：
2015-06-04
期刊：
影响因子：
16
通讯作者：
Rajewsky, Nikolaus
中科院分区：
文献类型：
--
作者：
Rybak-Wolf, Agnieszka;Stottmeister, Christin;Rajewsky, Nikolaus
环状RNA（circRNA）是一类内源性的动物RNA。尽管它们丰富，但它们在神经系统中的功能和表达是未知的。因此，我们对来自不同脑区、初级神经元、分离的突触以及神经元分化期间的RNA进行了测序。利用这些和其他可用的数据，我们发现并分析了数千种人类和小鼠神经元circRNA。circRNA在哺乳动物脑中非常丰富，序列保守，在人和小鼠中经常表达为circRNA，有时甚至在果蝇脑中检测到。circRNA在神经元分化过程中整体上调，在突触中高度富集，并且与其mRNA同种型相比通常差异表达。circRNA的表达与RNA编辑酶ADAR 1的表达呈负相关。ADAR 1的敲低诱导circRNA表达升高。总之，我们提供了一个circRNA脑表达图谱和重要的circRNA功能和价值作为生物标志物的证据。
Circular RNAs (circRNAs) are an endogenous class of animal RNAs. Despite their abundance, their function and expression in the nervous system are unknown. Therefore, we sequenced RNA from different brain regions, primary neurons, isolated synapses, as well as during neuronal differentiation. Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their mRNA isoforms. circRNA expression correlated negatively with expression of the RNA-editing enzyme ADAR1. Knockdown of ADAR1 induced elevated circRNA expression. Together, we provide a circRNA brain expression atlas and evidence for important circRNA functions and values as biomarkers.