Xu Kaiyu, Chen Dong, Wang Zhengbo, Ma Jian, Zhou Jian, Chen Nanhui, Lv Longbao, Zheng Yongtang, Hu Xintian, Zhang Yi, Li Jiali
1Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223 China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, 650223 China.
Cell Discov. 2018 Sep 18;4:48. doi: 10.1038/s41421-018-0050-1. eCollection 2018.
The abundance and function of circular RNAs (circRNAs) in mammalian brain have been reported, but their alterations in the biology of brain aging remain elusive. Here, using deep RNA profiling with linear RNA digestion by RNase R we explored a comprehensive map of changes in circRNA expression in rhesus macaque () brain in two age groups from adult (10 y) to aged (20 y) periods. Total 17,050 well expressed, stable circRNAs were identified. Cluster analysis reveals that dynamic changes in circRNA expression show the spatial-, sex- and age-biased specificities. On the basis of separate profiling of the RNAs, age-related circRNAs show differential correlation to host mRNA expression. Furthermore, two voltage-dependent L- and R-type calcium channel gene-derived circCACNA2D1 and circCACNA1E negatively regulate their host mRNA expression. Our results demonstrate the power of changes in circRNA expression to reveal insights into a potentially circRNA-mediated regulatory mechanism underlying the biology of brain aging.
哺乳动物大脑中环状RNA(circRNAs)的丰度和功能已有报道,但其在大脑衰老生物学中的变化仍不清楚。在此,我们通过用RNase R进行线性RNA消化的深度RNA分析,探索了成年(10岁)到老年(20岁)两个年龄组恒河猴大脑中circRNA表达变化的综合图谱。共鉴定出17,050个表达良好、稳定的circRNAs。聚类分析表明,circRNA表达的动态变化表现出空间、性别和年龄偏向的特异性。基于RNA的单独分析,与年龄相关的circRNAs与宿主mRNA表达显示出不同的相关性。此外,两个电压依赖性L型和R型钙通道基因衍生的circCACNA2D1和circCACNA1E负向调节其宿主mRNA表达。我们的结果证明了circRNA表达变化揭示大脑衰老生物学潜在的circRNA介导调控机制的能力。