Internal proofreading mechanisms in pre-mRNA splicing. (A) Involvement of splicing ATPases in multiple checkpoints of the splicing pathway. Shown are the spliceosome assembly pathway and the ATPase activities that are involved in checkpoints for incorrectly selected branchpoints (Prp5p, Prp16p) or splice sites (Prp16p, Prp22p, Prp43p), and which trigger a discard pathway. In the case of Prp22, a possible checkpoint of the 5′ splice site is indicated based on genetic evidence that Prp22p mutants can also promote the use of mutated 5′ splice sites. (B) Kinetic proofreading by splicing ATPases. In both cases, the proofreading activity ensures that the rate of the forward reaction is slower than the rate of the rejection reaction in the cases of aberrant substrates.
