Figure 4: A model of disrupted SNRPB regulation in CCMS.
From: Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro–costo–mandibular syndrome
Unknown repressor proteins (red circles) bind the ESS regulatory sequences (red squares) in the alternatively spliced exon (in blue) of SNRPB. Their binding leads to exclusion of this alternative exon, and thus an increase of SmB/SmB′ protein levels. Higher levels of these proteins then favour inclusion of the alternative exon, by an unknown mechanism, leading to NMD and a reduction of SmB/SmB′ protein levels. In alleles mutated in CCMS patients, the binding of repressor proteins is thought to be abolished or reduced due to the mutations present in the regulatory sequences. This leads to continued inclusion of the alternative exon, and reduced SmB/SmB′ protein levels due to NMD.
