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Quality control of gene expression:
mechanisms for recognition and elimination of nonsense mRNA in mammalian cells

Complex industrial manufacturing processes require multiple quality control checks along the assembly line to ensure a high proportion of properly functioning final products. Similarly, multiple quality control systems have evolved to recognize mistakes in the intricate chain of complicated biochemical reactions that are involved in the correct expression of the genetic information in each of our cells. Among those, “nonsense-mediated mRNA decay” (NMD) represents quality control mechanism that recognizes and rapidly degrades mRNAs of which the protein coding sequence is truncated by the presence of a premature termination codon (PTC). By eliminating these defective, so-called nonsense mRNAs with crippled protein-coding capacity, NMD substantially reduces the synthesis of potentially deleterious truncated proteins in the cell. Given that about 30% of all known disease-causing mutations in humans lead to the production of a nonsense mRNA, NMD serves as an important modulator of the clinical manifestations of genetic diseases, and manipulating NMD therefore represents a promising strategy for future therapies of many genetic disorders. However, the underlying molecular mechanisms of NMD are currently not well understood.


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