应对mRNA突变：转录适应机制与治疗潜力

Messenger RNAs (mRNAs) with a premature stop codon or with a lack of any stop codon are degraded in the cytoplasm by nonsense-mediated mRNA decay (NMD) or nonstop decay (NSD) machineries, respectively, producing mRNA decay fragments. Interleukin enhancer-binding factor 3 (ILF3) may bind some of these fragments and escort them to the nucleus. In a process of feedback transcriptional adaptation, ILF3–mRNA decay fragment complexes hybridize to complementary nuclear antisense RNAs produced by the mutated gene, which stimulates gene transcription. In a mechanism of feedforward transcriptional adaptation, ILF3–mRNA decay fragment complexes can also hybridize with antisense or regulatory RNAs produced by other adapting genes (i.e., paralogs or functionally related genes, respectively), stimulating their transcription. …