Figure 2.

Splicing of pre-mRNA into mature mRNA. (a) Overview of different complexes in the spliceosome. (b) Splicing in wild-type SF3B1 (SF3B1^WT) cells: SF3B1^WT binds to the branchpoint of the pre-mRNA, usually an adenosine. When this process is executed correctly, mature mRNA is formed which results in a canonical protein. (c) Splicing in mutated SF3B1 (SF3B1^MUT) cells: SF3B1^MUT recognizes an alternative branchpoint, which leads to mis-splicing of the mRNA (e.g., intron retention, exon skipping and intronic extension of exon). The mis-spliced mRNA can be translated into aberrant proteins or be degraded by nonsense-mediated decay (NMD), resulting in downregulation of gene expression.