Post-transcriptional regulation of allele-specific expression

Allele-specific expression (ASE) serves as a unique readout for understanding how genetic and epigenetic variations fine-tune gene regulation in diploid organisms. While allelic transcriptional control mediated by cis-elements and epigenetic marks has been extensively characterized, how these allele-specific effects propagate through the post-transcriptional landscape remains less understood. In this review, we synthesize emerging evidence of allele-specific regulation throughout the RNA life cycle, spanning RNA structure, RNA-binding protein recognition, splicing, polyadenylation, translation, and decay. Crucially, we highlight the epitranscriptomic layer, specifically N⁶-methyladenosine (m⁶A) and A-to-I editing, as a pivotal mechanism bridging genetic or epigenetic variation to ASE. We discuss recent findings of widespread sequence-dependent m⁶A and, notably, parent-of-origin-dependent m⁶A, which suggests a novel epigenomic-to-epitranscriptomic imprint transmission mechanism. Finally, we explore how long-read sequencing technologies are offering a multidimensional perspective on ASE regulation.