Yang Jian, Jin Nana, Zhang Shuqiang, Tan Ya, Chen Zhifeng, Huang Xiaoli, Li Guicai, Yu Bin, Shi Jianhua, Gu Xiaosong, Cui Zhiming, Xu Lian
Department of Neurosurgery, People's Hospital of Deyang City, Sichuan Clinical Research Center for Neurological Diseases, Deyang, Sichuan, China.
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu, China.
Cell Mol Life Sci. 2025 Apr 1;82(1):135. doi: 10.1007/s00018-025-05665-1.
Circular RNAs (circRNAs) have re-emerged as promising gene regulators in various physiological and pathological conditions. However, the expression patterns of circRNAs in the developing spinal cord of mammals and the comprehensive distribution of circRNAs across different tissues remain poorly understood. In this study, rats were used as the model organism. We conducted a comprehensive analysis of 15 RNA-Seq datasets comprising 217 rat samples and developed a web-based resource, CiRNat, to facilitate access to these data. We identified 15,251 credible circRNAs and validated them through experimental approaches. Notably, we observed two significant time points for circRNA increase during spinal cord development, approximately at embryonic day 14 (E14d) and postnatal week 4 (P4w). Analysis of circRNA expression in various rat tissues revealed higher expression levels in central nervous system tissues compared to peripheral nervous system tissues and other tissues. Furthermore, some highly abundant circRNAs exhibited tissue- and species-specific expression patterns and differed from their cognate linear RNAs, such as those derived from Gigyf2. Integrating polysome profiling and bioinformatic predictions suggested potential functions of certain circRNAs as miRNA sponges and translational templates. Collectively, this study provides the first comprehensive landscape of circRNAs in the developing spinal cord, offering an important resource and new insights for future exploration of functional circRNAs in central nervous system development and related diseases.
环状RNA（circRNAs）已再度成为各种生理和病理条件下有前景的基因调控因子。然而，circRNAs在哺乳动物发育中的脊髓中的表达模式以及circRNAs在不同组织中的全面分布仍知之甚少。在本研究中，大鼠被用作模式生物。我们对包含217个大鼠样本的15个RNA测序数据集进行了全面分析，并开发了一个基于网络的资源CiRNat，以方便获取这些数据。我们鉴定出15251个可靠的circRNAs，并通过实验方法对其进行了验证。值得注意的是，我们观察到在脊髓发育过程中circRNA增加的两个重要时间点，大约在胚胎第14天（E14d）和出生后第4周（P4w）。对各种大鼠组织中circRNA表达的分析表明，与外周神经系统组织和其他组织相比，中枢神经系统组织中的表达水平更高。此外，一些高丰度的circRNAs表现出组织和物种特异性的表达模式，并且与其同源线性RNA不同，例如源自Gigyf2的那些。整合多核糖体分析和生物信息学预测表明某些circRNAs作为miRNA海绵和翻译模板的潜在功能。总的来说，本研究提供了发育中脊髓中circRNAs的首个全面概况，为未来探索中枢神经系统发育和相关疾病中的功能性circRNAs提供了重要资源和新见解。
