Post-transcriptional regulatory mechanisms of dosage compensation in vertebrates

Sex chromosome dosage compensation is thought to be essential in species with heteromorphic sex chromosomes. There has been a large emphasis on transcriptional regulation as the primary mechanism restoring gene dosage balance. However, emerging evidence across vertebrate lineages indicates that post-transcriptional mechanisms make critical contributions to balancing X/Z gene dosage in the proteome. Here, we propose potential mechanisms that may be responsible for this post-transcriptional regulation, including nonsense mediated decay (NMD), N6-methyladenosine RNA methylation (m6A) and sex specific micro-RNAs (miRNAs). We propose that multi-layered regulation of sex chromosome dosage is an ancient and widespread strategy. Recognizing the role of post-transcriptional processes not only reframes current models of dosage compensation, but also uncovers novel mechanisms underpinning development, reproduction and disease.