The anatomy of a PTM. The figure depicts a mutant target pre-mRNA (see the LacZ model system in ref. 12) that is incapable of coding for functional protein because it contains a mutation in the second exon (indicated as orange segment). The product of the conventional cis-splicing reaction for this pre-mRNA is a defective mRNA. The PTM shown contains several domains. The binding domain (also referred to as the targeting domain) binds to the pre-mRNA target, thus localizing the PTM near the site of the desired trans-splicing reaction. The binding domain can also be designed to occlude important elements within the 3′ splice site of the target and thus reduce the cis-splicing reaction. Between the binding domain and the trans-splicing domain there is usually a spacer region for flexibility. The trans-splicing domain, which in the case shown includes the elements required to make a potent 3′ splice site, is responsible for the reactivity of the PTM. Finally, the coding domain contains the necessary genetic information that will be imparted into the reprogrammed RNA. This can include protein-coding instructions as well as instructions for the effective processing, transport, and localization of the reprogrammed mRNA. In the example shown, the open reading frame has been changed to repair the mutation in the gene, and the 3′ untranslated region (3′ UTR) has been enhanced to increase mRNA stability and translation. It should be noted that the cis- and trans-splicing reactions are in competition. This implies that as the level of reprogrammed mRNA increases, the level of defective mRNA decreases. A decrease in the level of defective mRNA may be very useful in the case of dominant mutations.