摘要
环状RNA(circRNA)是一类特殊的呈闭合环状结构的非编码RNA,参与多种生物学过程,如细胞增殖、分化和凋亡,在多种疾病发生中发挥重要作用,同时也是潜在的生物标志物和治疗靶点。为探索circRNA对病毒复制的影响,本研究对HY12肠道病毒感染MC38细胞的circRNA差异表达进行了组学测定与分析,发现在HY12病毒感染后有570个circRNA表达水平上调,381个circRNA表达水平下调。在570个表达上调的circRNA中,选择差异显著上调的circRNA mmu_circ_0001083为研究对象,探讨其与HY12感染之间的关联以及对病毒复制的影响。结果显示,HY12病毒感染细胞后,宿主环状RNA mmu_circ_0001083的表达显著上升,且其表达水平呈现病毒剂量与时间依赖性。与感染正常MC38细胞相比,HY12病毒感染环状RNA mmu_circ_0001083敲低的MC38细胞后,其2C蛋白表达减少,病毒滴度显著降低。相反,HY12病毒感染过表达环状RNA mmu_circ_0001083的MC38细胞后,其2C蛋白表达增加,病毒滴度明显升高。上述结果表明,宿主环状RNA mmu_circ_0001083的表达上调与HY12病毒感染复制呈显著正相关,即mmu_circ_0001083对HY12的复制起到了正向调控的作用,该结果为今后深入研究环状RNA对HY12病毒复制的调控机制打下基础。
Circular RNA(circRNA)represents a unique class of closed-loop structured non-coding RNAs involved in various biological processes such as cell proliferation,differentiation,and apoptosis.They play a significant role in the development of numerous diseases,and also serve as potential biomarkers and therapeutic targets.To explore the impact of circRNA on viral replication,this study performed an omics measurement and analysis of circRNA differential expression in MC38 cells infected with HY12 enterovirus.It was found that,following HY12 virus infection,the expression levels of 570 circRNAs were upregulated,while 381 circRNAs were downregulated.Among the upregulated circRNAs,the significantly upregulated circRNA mmu_circ_0001083 was selected for further investigation into its association with HY12 infection and its impact on viral replication.The results indicated that after HY12 virus infection,the expression of host circRNA mmu_circ_0001083 significantly increased,and its expression level was dependent on the virus dosage and time.Compared to normal MC38 cells infected with the HY12 virus,cells with knocked down expression of circRNA mmu_circ_0001083 showed reduced expression of the 2C protein and significantly lower viral titers.Conversely,after HY12 virus infection in MC38 cells with overexpressed circRNA mmu_circ_0001083,there was an increase in the expression of the 2Cprotein and a significant rise in viral titers.These results suggest that the upregulation of host circRNA mmu_circ_0001083is significantly positively correlated with the replication of HY12virus,meaning mmu_circ_0001083plays a positive regulatory role in the replication of HY12.This finding lays a foundation for future in-depth studies on the regulatory mechanisms of circRNA on viral replication.
作者
张芷源
张群
章凡
崔续媛
郑学博
胡俊英
常晓冉
张福慧
王新平
ZHANG Zhiyuan;ZHANG Qun;ZHANG Fan;CUI Xuyuan;ZHENG Xuebo;HU Junying;CHANG Xiaoran;ZHANG Fuhui;WANG Xinping(State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases/Key Laboratory for Zoonosis Research of the Ministry of Education,College of Veterinary Medicine,Jilin University,Changchun 130062,China)
出处
《中国兽医学报》
CAS
CSCD
北大核心
2024年第8期1629-1638,共10页
Chinese Journal of Veterinary Science
基金
“十三五”国家重点研发计划资助项目(2017YFD0500104,2016YFD0500904)。