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Preventing Dangerous Nonsense: Selection for Robustness to Transcriptional Error in Human Genes

Figure 3

Intragenic depletion of fragile codons commences beyond the boundary of EJC–dependent NMD activity.

Normalized fragile codon usage (NFCU) in “NMD-competent” and “NMD-compromised” regions of multi-exon genes. The schematic depicts a generic mammalian mature mRNA. The arrowhead shows the position of the last exon-exon junction. The relative efficiency of each mammalian NMD pathway predicted in three distinct regions is shown using ‘+’ symbols. Predicted inactivity of NMD is shown using a ‘-’ symbol. EJC-dependent NMD is expected to be active >50–55 nts 5′ of the last exon-exon junction and inactive 3′ of the last exon-exon junction. Its activity is uncertain in the intervening 50–55 nts region (hatched shading). PABP-dependent NMD is expected to increase in efficiency with distance from the poly-A tail. Note that the efficiency of PABP-dependent NMD is predicted to be much lower than that of EJC-dependent NMD. NFCU was determined in two windows of 50 codons positioned on either side of the last exon-exon junction. The example shows the last intron in “phase 0” (i.e. the intron is positioned between codons) and the depicted nucleotide coordinates for each window are specific to this case.

Figure 3