Emerging role of alternative splicing in oral and maxillofacial development

Abstract

The excision of introns and subsequent ligation of exons in precursor messenger RNA (pre-mRNA) is a fundamental mechanism requisite for the expression of eukaryotic genes. Alternative splicing (AS) serves as a potent amplifying factor, augmenting the spectrum of protein isoforms that can emanate from a singular genetic locus, thereby bolstering proteomic diversity. Perturbations in the regulatory framework of pre-mRNA splicing have been associated with an extensive array of pathological conditions. Oral and maxillofacial morphogenesis, a multifaceted process governed by intricate molecular interactions during embryonic development, is also susceptible to the modulating influence of alternative splicing. Aberrations or dysfunctions in the components responsible for alternative splicing during this critical developmental window can culminate in abnormal craniofacial architectures. In this scholarly review, our emphasis is placed on the exploration of RNA splicing as an emergent feature in oral and maxillofacial development. Importantly, we spotlight instances of splicing dysregulation that contribute to either non-syndromic or syndromic manifestations of cleft palate and enamel developmental anomalies. Deepening our understanding of the role of RNA splicing components and potential downstream effectors in oral and maxillofacial development may provide invaluable insights for prenatal diagnostic modalities.