Figure 1. a. Impact of UPF1 on the decay of PTC-mRNAs in HCT116 cells.

TGFBR2, SLC35F5, ARV1, MSH3, SMAP1, TTC3, EFHC1, MBD4, WDR19, BAX, RECQL, RAD50 and MSH6 harbor homozygous or heterozygous frameshift mutations in the HCT116 MSI CRC cell line. Using expression array, fold changes in the expression of the corresponding mRNAs relative to UPF1 silencing were determined (fold change = E_mRNA in cells treated with a UPF1 siRNA / E_mRNA in cells treated with control siRNA). Genes that are underlined are those whose re-expression was significant in these conditions (1.5 fold-change up with a p-value ≤0.005). Evidence for variable sensitivity to UPF1-mediated decay of such PTC-mRNAs could therefore be obtained, although allele specific expression assays were not used to differentiate between mutated and wild-type mRNAs in the case of heterozygous frameshift alterations. b. Coding frameshift mutations in target genes relative to NMD-status in MSI primary CRCs. Frequencies of frameshift mutations of the same series of 13 target genes for instability in 44 MSI primary CRCs are represented. Target genes whose frameshift mutations are frequently selected for during MSI CRC progression harbor different sensitivities to UPF1-mediated decay.