PDF(Pubmed)
Abstract：
We previously showed that stroke alters circular RNA (circRNA) expression profiles. Many circRNAs undergo epitranscriptomic modifications, particularly methylation of adenosine to form N6-methyladenosine (m6A). This modification significantly influences the circRNA metabolism and functionality. Hence, we currently evaluated if transient focal ischemia in adult C57BL/6J mice alters the m6A methylation of circRNAs. Changes in m6A were profiled in the peri-infarct cortex following immunoprecipitation coupled with microarrays. Correlation and gene ontology analyses were performed to understand the association of m6A changes with circRNA regulation and functional implications after stroke. Many circRNAs showed differential regulation (up or down) after stroke, and this change was highest at 24h of reperfusion. Notably, most circRNAs differentially regulated after stroke also exhibited temporal changes in m6A modification patterns. The majority of circRNAs that showed post-stroke differential m6A modifications were derived from protein-coding genes. Hyper-than hypomethylation of circRNAs was most prevalent after stroke. Gene ontology analysis of the host genes suggested that m6A-modified circRNAs might regulate functions such as synapse-related processes, indicating that m6A epitranscriptomic modification in circRNAs could potentially influence post-stroke synaptic pathophysiology.
摘要：
我们先前表明，中风会改变环状RNA（circRNA）表达谱。许多circRNAs经过表观基因组修饰，特别是腺苷的甲基化以形成N6-甲基腺苷(m6A)。这种修饰显著影响circRNA代谢和功能。因此，我们目前评估了成年C57BL/6J小鼠的短暂性局灶性缺血是否改变了circRNAs的m6A甲基化。免疫沉淀结合微阵列后，梗死周围皮质中m6A的变化进行了分析。进行相关性和基因本体论分析以了解m6A变化与circRNA调节和卒中后功能意义的关联。许多circRNAs在中风后表现出差异调节（上升或下降），这种变化在再灌注24h时最高。值得注意的是,卒中后大多数差异调节的circRNAs也表现出m6A修饰模式的时间变化。显示中风后差异m6A修饰的大多数circRNAs来自蛋白质编码基因。中风后circRNAs的超甲基化比低甲基化最普遍。宿主基因的基因本体论分析表明，m6A修饰的circRNAs可能调节突触相关过程等功能。表明circRNAs中的m6A表位转录组修饰可能会影响卒中后突触病理生理学。
