Stroke triggers dynamic m 6 A reprogramming of cerebral circular RNAs.

We previously showed that stroke alters circular RNA (circRNA) expression profiles. Many circRNAs undergo epitranscriptomic modifications, particularly methylation of adenosine to form N ⁶ -methyladenosine (m ⁶ A). This modification significantly influences the circRNA metabolism and functionality. Hence, we currently evaluated if transient focal ischemia in adult C57BL/6J mice alters the m ⁶ A methylation of circRNAs. Changes in m ⁶ A were profiled in the peri-infarct cortex following immunoprecipitation coupled with microarrays. Correlation and gene ontology analyses were performed to understand the association of m ⁶ A 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 m ⁶ A modification patterns. The majority of circRNAs that showed post-stroke differential m ⁶ A 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 m ⁶ A-modified circRNAs might regulate functions such as synapse-related processes, indicating that m ⁶ A epitranscriptomic modification in circRNAs could potentially influence post-stroke synaptic pathophysiology.
Competing Interests: Declaration of competing interest None.
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