Method for identifying interventions that control the translational activity of ribosomal proteins in differential mRNA expression

A screening system for a compound that ameliorates or reverts a defective or undesired translational read-through of a target gene bearing a premature termination codon (PTC) in a eukaryotic cell, the screening system comprising a recombinant eukaryotic cell

• a) expressing a recombinant ribosome comprising a ribosomal protein having a deletion or other mutation that causes a defective or undesired translational read-through of a PTC-bearing target gene,
• b) expressing a first reporter construct comprising said PTC-bearing target gene coupled to a gene encoding a first reporter group that is co-expressed with said PTC-bearing target gene,
• c) expressing a second reporter construct comprising a gene encoding a second reporter group that is expressed independently from said PTC-bearing target gene as an internal standard,
• wherein the first reporter construct and the second reporter construct are both expression cassettes or both expression vectors,
• wherein said first and second reporter groups are independently selected from fluorescent protein reporter molecules, bioluminescent protein reporter molecules, maltose binding protein, phosphatase, peroxidase, kinase, chloramphenicol transferase, and β-galactosidase,
• wherein said PTC-bearing target gene is selected from the group consisting of a LAMB3 gene and a CYH2 gene, and
• wherein said ribosomal protein is selected from the group consisting of rPL19A, rPL25, and rPL10.