Table 4.
Pathologies resulting from a change in mRNA structure which selectively abolishes production of the long or short form of a transcription factor
| Gene | Translational mechanism that normally generates two protein isoforms | Disease-associated change in mRNA structure and translation | References |
|---|---|---|---|
| C/EBPα (human) | Two proteins from one mRNA via leaky scanning+reinitiation shunt | In acutemyeloidleukemia, mutations near amino terminus eliminate production of longer isoform. | Pabst et al., 2001 |
| GATA1 (human) | Two proteins from one mRNA via leaky scanning | In Downsyndrome-relatedleukemia, premature stop codon eliminates production of longer isoform. | Wechsler et al., 2002 |
| LEF1 (human) | Two proteins from two mRNAs (via two promoters) | In coloncancer, failure to activate downstream promoter prevents production of shorter (inhibitory) isoform. | Hovanes et al., 2001 |
| Rx/rax (mouse) | Two proteins from one mRNA via leaky scanninga | In eyeless mice, mutation of second AUG, leaving only the weak upstream start codon, results in inadequate yield. | Tucker et al., 2001 |
a
Here the long and short isoforms appear to function identically; the significance of the second AUGSTART codon pertains to boosting the overall protein yield. The eyeless mouse serves as a spontaneous model for human anophthalmia.