Figure 7. Model for SUGP1-DHX15 and proofreading at early spliceosome assembly.
Left panel: On weak splice sites the transition from E complex to A complex is inhibited as PB binds to the U2 snRNP and prevents the full binding of the branch helix and recognition of the BP-A. These stalled spliceosomes are recognized by SUGP1-DHX15 and are discarded. Less mRNA is being produced in this scenario and more alternatively spliced mRNAs result.
Right panel: Mutation in SUGP1 weakens SUGP1 interaction with DHX15, removing the proofreading & discard pathway, allowing more time to assemble A complex and to proceed with splicing.