Schematic representation of the concept of cotranscriptional RNA splicing and potential outcomes of mutations of genes encoding proteins of the spliceosome. Top: Although transcription of nucleosome-free DNA into pre-mRNA by RNA polymerase II and pre-mRNA splicing are traditionally considered as separate and sequential processes, increasing evidence suggests that transcription and RNA processing are strictly coupled in vivo and that several splicing factors also play a role in the regulation of transcription. According to Han et al,⁹  cotranscriptional splicing represent a general rule with exceptions. Bottom: Potential outcomes of mutations of genes encoding proteins of the spliceosome. These outcomes include reduced (or also increased) transcription, exon skipping, intron retention, and cryptic exonic (or intronic) splice site activation with truncated (or elongated) exon. Adapted from Ebert and Bernard.⁴