In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess a single X chromosome, while females (XX) undergo X inactivation. To compensate for this reduction in dosage compared with two active copies of autosomes, it has been proposed that genes from the active X chromosome exhibit dosage compensation. However, the existence and mechanisms of X-to-autosome dosage compensation are still under debate. Here we show that X-chromosomal transcripts have fewer m⁶A modifications and are more stable than their autosomal counterparts. Acute depletion of m⁶A selectively stabilizes autosomal transcripts, resulting in perturbed dosage compensation in mouse embryonic stem cells. We propose that higher stability of X-chromosomal transcripts is directed by lower levels of m⁶A, indicating that mammalian dosage compensation is partly regulated by epitranscriptomic RNA modifications.

在哺乳动物中，X 染色体基因由单个拷贝表达，因为雄性 (XY) 拥有单个 X 染色体，而雌性 (XX) 则经历 X 失活。为了补偿与两个活性常染色体拷贝相比剂量的减少，有人提出来自活性 X 染色体的基因表现出剂量补偿。然而，X-常染色体剂量补偿的存在和机制仍存在争议。在这里，我们表明 X 染色体转录本具有较少的 m ⁶ A 修饰，并且比常染色体转录本更稳定。m ⁶ A 的急性消耗选择性地稳定常染色体转录物，导致小鼠胚胎干细胞中的剂量补偿受到干扰。我们提出 X 染色体转录物的较高稳定性是由较低水平的 m ⁶ A 引导的，这表明哺乳动物的剂量补偿部分受到表观转录组 RNA 修饰的调节。