Figure 3. A PTC in a Coding Region Typically Elicits a Translation-Dependent Surveillance Mechanism, Such As NMD, Which Leads to the Degradation of the Aberrant Transcript.

If the mRNA region containing the PTC harbors fortuitous recognition elements for its spliceosome-mediated removal (e.g., latent splice sites), a PTC-containing segment may be spliced out during mRNA maturation (in grey). The likelihood with which accidental splicing of an entirely new intron may occur is expected to be higher in regions of the transcript where the concentration of SFs is naturally elevated (e.g., at the 5′ end, in proximity of the CBC), compared to the mRNA 3′ end, where strong canonical termination signals (in orange) favor the preferential binding of CPFs that, under the proposed model, compete/interfere with SFs for the binding of U-rich tracts. The fortuitous gain of introns is favored at the 5′ end because unspliced PTC-containing transcripts in this region are more efficiently degraded, thereby alleviating the negative cellular consequences of the PTC.