RNA stability controlled by mA methylation contributes to X-to-autosome dosage compensation in mammals.

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 mA modifications and are more stable than their autosomal counterparts. Acute depletion of mA 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 mA, indicating that mammalian dosage compensation is partly regulated by epitranscriptomic RNA modifications.