Nanopore Detection of METTL3-Dependent m6A-Modified mRNA Reveals a New Mechanism Regulating Cardiomyocyte Mitochondrial Metabolism

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mRNA contains chemical modifications that can alter its processing and contribute to known discrepancies between transcript and protein abundances.Traditional/indirect RNA sequencing requires the conversion of RNA into cDNA and fails to detect most RNA modifications.Nanopore technology is a form of direct sequencing that reads native RNA and informs on modifications like N6-methyladenosine (m6A).m6A is formed by enzymes such as Methyltransferase Like Protein 3 (METTL3), increases with hypertrophic cardiac stimuli 1 and in the myocardium of heart failure patients 2-4 , and regulates cardiac homeostasis 1 .Here, we used Nanopore sequencing to detect high fidelity METTL3dependent m6A sites that influence cardiomyocyte function.

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