N⁶-methyladenosine (m⁶A) 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 m⁶A-positive and m⁶A-negative RNA populations. Both the presence and extent of A-to-I sites in m⁶A-negative RNA transcripts suggest a negative correlation between m⁶A and A-to-I. Suppression of m⁶A-catalyzing enzymes results in global A-to-I RNA editing changes. Further depletion of m⁶A modification increases the association of m⁶A-depleted transcripts with adenosine deaminase acting on RNA (ADAR) enzymes, resulting in upregulated A-to-I editing on the same m⁶A-depleted transcripts. Collectively, the effect of m⁶A on A-to-I suggests a previously underappreciated interplay between two distinct and abundant RNA modifications, highlighting a complex epitranscriptomic landscape.

N ⁶ -甲基腺苷(m ⁶ A) 和腺苷转肌苷 (A-to-I) 编辑是两种最丰富的 RNA 修饰，均位于腺苷上。然而，这两种类型的腺苷修饰的相互作用在很大程度上是未知的。在这里，我们展示了 m ⁶ A 阳性和 m ⁶ A 阴性 RNA 群体之间的全局 A-to-I 差异。m ⁶ A 阴性 RNA 转录物中 A-to-I 位点的存在和范围均表明 m ⁶ A 和 A-to-I之间存在负相关。抑制 m ⁶ A 催化酶导致全局 A-to-I RNA 编辑变化。m ^{6 的}进一步消耗A 修饰增加了 m ^{6 的结合}腺苷脱氨酶作用于 RNA (ADAR) 酶的 A 耗尽转录本，导致在相同的 m ⁶ A 耗尽转录本上上调 A-to-I 编辑。总的来说，m ⁶ A 对 A-to-I 的影响表明，两种不同且丰富的 RNA 修饰之间存在先前未被充分认识的相互作用，突出了复杂的表观转录组学景观。