A novel m7G RNA methylation-related signature associated with MAPK signaling pathways in acute ischemic stroke

Abstract

Objectives Ischemic stroke represents a major global cause of disability and death. Timely recanalization of occluded vessels to salvage the ischemic penumbra is the cornerstone of acute ischemic stroke (AIS) treatment. Nevertheless, the molecular mechanisms driving the transition from salvageable penumbra to infarct core in early AIS remain poorly understood. Recent evidence highlights the role of post-transcriptional methylation, especially N7-methylguanosine (m7G) modification, in stroke pathogenesis. This study aimed to systematically characterize transcriptome-wide m7G methylation changes in the ischemic penumbra during early AIS and to explore their potential functional relevance. Methods We performed middle cerebral artery occlusion in 8-week-old male BALB/c mice and applied MeRIP-seq to profile the transcriptome-wide m7G methylome in penumbra tissue. Bioinformatics analyses were conducted to elucidate the functional relevance of m7G-methylated transcripts. Results Compared with controls, AIS penumbra exhibited significant alterations in m7G-modified mRNAs. Specifically, upregulated m7G modifications were notably enriched in mRNAs associated with the mitogen-activated protein kinase (MAPK) signaling pathway, whereas downregulated modifications were significantly linked to axon guidance pathways. Conclusions This study provides the first systematic landscape of m7G methylation in AIS and m7G RNA methylation-related alterations in the MAPK signaling pathway may serve as potential therapeutic targets for stroke intervention.