Spliceosome complex and neurodevelopmental disorders

Neurodevelopment requires complex spatiotemporal expression, which heavily relies on proper RNA splicing. The spliceosome is a ribonucleoprotein complex that removes introns from pre-mRNA, joins exons, and produces mature mRNA. Pathogenic variants in genes that code for spliceosome RNAs and proteins cause RNA mis-splicing and spliceosomopathies. Splicing defects during nervous system development upend the tightly controlled neurodevelopmental process, leading to neurodevelopmental disorders (NDDs). Despite the fact that the spliceosome is expressed in every cell, not all spliceosomopathies present as NDDs; spliceosomopathies are often tissue-specific in that a variant has a greater impact on certain cell lineages or cell types. Here we discuss spliceosomopathies whose presentations include NDDs and focus on spliceosome-coding genes.