N-Methyladenosines Modulate A-to-I RNA Editing.

N-methyladenosine (mA) and adenosine-to-inosine (A-to-I) editing are two of the most abundant RNA modifications, both at adenosines. Yet, the interaction of these two types of adenosine modifications is largely unknown. Here we show a global A-to-I difference between mA-positive and mA-negative RNA populations. Both the presence and extent of A-to-I sites in mA-negative RNA transcripts suggest a negative correlation between mA and A-to-I. Suppression of mA-catalyzing enzymes results in global A-to-I RNA editing changes. Further depletion of mA modification increases the association of mA-depleted transcripts with adenosine deaminase acting on RNA (ADAR) enzymes, resulting in upregulated A-to-I editing on the same mA-depleted transcripts. Collectively, the effect of mA on A-to-I suggests a previously underappreciated interplay between two distinct and abundant RNA modifications, highlighting a complex epitranscriptomic landscape.